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Humans and Hardware: How Special Operations Can Pioneer Wearable Technology – War on the Rocks
Posted: November 5, 2021 at 9:45 pm
In 2009, the U.S. Special Operations Command announced that Humans are more important than hardware. But with wearables revolutionizing sports medicine and athletics, the distinction between humans and hardware is less relevant than ever. This means that investing in wearable technology for special operations forces is now the best way to put humans first.
What might this look like? With a small population of elite warfighters in high-stress environments, Special Operations Command can lead the force in determining which wearable devices are worth the investment. The Preservation of the Force and Family program, which is already in place to improve the holistic health of special operations forces, can spearhead efforts to distribute, monitor, test, and best utilize wearables for the entire military.
A Wearable Revolution
In the last two decades, sports medicine and sports science have advanced dramatically. Athletes are now bigger, faster, and stronger due, in part, to advancements in technologies that allow them to train smarter. A critical facet of this revolution is wearable technology that offers athletes immediate and continuous feedback on an increasing number of health and performance metrics. The wearable trend started with simple Global Positioning System-enabled devices measuring steps taken in a day and heart-rate monitors allowing users to train in specific heart-rate zones. However, wearable technology is now quickly outpacing older, more expensive, and more invasive technologies. New Apple Watches, for example, allow users to bypass hospital visits by serving as both an electrocardiogram to monitor heart health and a pulse oximeter to measure blood oxygen levels in 10 seconds. Wearables rapid development is providing valuable new tools for physical therapists and healthcare professionals and eliciting optimism about the future of individualized self-care.
This revolution hasnt gone unnoticed by the Department of Defense, which is testing wearables across different military branches. The U.S. Air Force recently began using the Oura Ring, a technology worn on your finger, to more accurately determine pilots flight readiness in the morning based on their overall sleep score. Previously, pilots flight readiness was determined by hours in bed rather than the quality of sleep. However, Oura Rings offer the ability to both measure sleep quality and potentially improve sleep, making pilots fitter to fly. Additionally, the U.S. Navy regularly tests various wearable devices at the Naval Postgraduate School Human and Systems Integration laboratory to study and improve crew rest, while the U.S. Army tests wearables to study soldiers resiliency in harsh winter conditions. As wearable technology continues to progress, so do the applications and opportunities to improve service members sleep, fitness, and overall health.
Wearables Potential in Special Operations
In 2012, Special Operations Command adopted the Preservation of the Force and Family strategy. The goal was to optimize and sustain mission readiness, longevity, and performance, thereby maximizing the estimated $1.5 million investment that the military makes in each member of special operations. The strategy seeks to provide precise preventative interventions and emphasisizes holistic health across five domains: physical, cognitive, psychological, social and family, and spiritual.
Wearable technology is already improving individual physical fitness and should be a critical component in enhancing operator health across every all of these domains. Wearables currently track a host of physical and biological metrics and use algorithms to generate useful approximations of additional metrics, including sleep quality, readiness, and stress. Many wearable interfaces offer coaching to nudge users towards healthier behaviors. Leading wearables, including the Oura Ring, Apple Watch, and Whoop Strap, offer nuanced sleep and activity coaching based on users unique metrics and trends. Put simply, wearables can tell you when you are overworked and need a break.
In an organization like Special Operations Command, which demands long hours under highly stressful conditions, having a tool that provides an objective measurement of readiness is uniquely valuable. Operators are specially selected and trained for resilience to adverse physical and mental conditions. Constant adaptation to a changing environment, however, comes at a cost. But this advantageous adaptation can produce allostatic load, leading to chronic physical maladies including pain, fatigue, and compromised immunity. Reduction of allostatic load first requires identification of increased stress. Enter wearables. Wearables can provide feedback on a host of biological metrics correlated with stress, including heart-rate variability, resting heart rate, and sleep quality. This makes it possible to identify chronic physiological stress, implement nuanced interventions, and prevent the difficulties associated with allostatic overload.
Wearables can also bring benefits in the cognitive and psychological domains. The Oura Ring encourages users to monitor body signals through practices such as guided mindfulness and breathing protocols. As shown by ongoing studies at Texas A&M, mindfulness meditations and associated breathing exercises can reduce stress and improve mental health. This can be particularly useful to special operations forces in reducing combat mental illness. Paired with blast gauge data or baseline cognitive tests such as the Automated Neuropsychological Assessment Metrics, wearables may also allow the early identification and treatment of traumatic brain injury.
Mitigating Concerns
In a profession where chronic stress is so abundant that it produced the term operator syndrome, why are wearable technologies not already commonplace? For one thing, there isnt a one-size-fits-all wearable. While one wearable specializes in sleep, for example, it may not be as effective at measuring physical activity. Concerns over operational security also dampen wearable enthusiasm in the Defence Department. And for good reasons in 2018, the fitness and location tracking application Strava infamously illuminated the location of multiple overseas military bases. Similarly, privacy risks regarding collected data can cause hesitation in an increasingly connected and data-driven world. Data security and patient confidentiality are paramount concerns with aggregated health information collected from wearables, and have legal implications under the Health Insurance Portability and Accountability Act. While data is routinely stripped of identifiers, including names and addresses, it can become re-identifiable when correlated with other datasets.
Special Operations Command has an important role to play in helping to address these security and privacy concerns. Letting the Preservation of the Force and Family program lead the development of wearables can help by removing military commanders from the loop, preventing mandatory use and giving participants the power of consent. Personnel associated with this program are also trained and certified to handle protected health information, reducing the risk of a Health Insurance Portability and Accountability Act violation and relieving military commanders of such a burden. Assigning random user identifications can help to avoid the disclosure of personal data. Preservation of the Force and Family personnel can further prevent the re-identification of anonymous users by isolating the wearables data, thereby preventing their merging with larger military data sets.
While there are simple ways to mitigate the known concerns over wearables, there will always be risks, especially with the early adoption of technology. These risks should be explored, preferably in a small and competent population, to best identify and understand wearables capabilities and limitations. Implementation and open dialogue will enable the force to exploit wearables significant potential to improve holistic health.
Wearables Are Coming!
In any technological revolution, there will be resistance to adopting new technology, especially in large organizations like Special Operations Command. Nevertheless, wearable technology has taken the world by storm. Large corporations have adopted wearables into healthcare policies, and wearable tech is an $81.5 billion industry. With a smaller population that is often presented with high chronic stress, Special Operations Command has the opportunity to lead the U.S. military in the use of wearable technology. By leveraging the recent revolution in wearables, programs such as Preservation of the Force and Family can bring humans and hardware together in the safest and smartest way possible.
Maj. Kevin Butler and Maj. Frank Foss are Army Special Forces officers currently pursuing a masters in Defense Analysis at the Naval Postgraduate School. Between them, they have over a dozen combat and operational deployments to the Central Command and Southern Command.
Disclaimer: The views expressed in this article are the views of the authors alone. They do not reflect the official position of the Naval Postgraduate School, the U.S. Army, the Department of Defense, or any other entity within the U.S. government and the authors are not authorized to provide any official position of these entities.
Image: U.S. Army (Photo by Sgt. Apolonia Gaspar)
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Humans and Hardware: How Special Operations Can Pioneer Wearable Technology - War on the Rocks
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Therapeutic Frontiers for Relapsed/Refractory Multiple Myeloma Expand With CAR T and Bispecific Antibodies – OncLive
Posted: at 9:45 pm
CAR T-cell therapy and bispecific antibodies for T-cell redirection are 2 recent immune strategies developed in the treatment of multiple melanoma.
Multiple Myeloma is a clonal plasma cell neoplasm characterized by bone lesions, renal impairment, cytopenias, and immunodeficiency. Despite significant therapeutic advancements in the past 2 decades that have resulted in improved survival, myeloma remains an incurable disease. The immune environment in which the cancer cells thrive is known to be a key player in the evolution of monoclonal gammopathies from premalignant stages to advanced malignancy. Further, immune dysregulationmarked by T-cell exhaustion, tolerance induction by tumor microenvironment, and tumor escape from immune surveillanceis important in the pathogenesis. Therefore, various immune strategies have been developed, including immune-enhancing drugs such as immunomodulatory drugs, checkpoint inhibitors, monoclonal antibodies, and, more recently, chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for T-cell redirection.
CAR T cells are T lymphocytes genetically modified by viral vectors or nonviral technology such as DNA transposons to express a synthetic receptor to target a specific antigen. The single chain variable fragment (ScFV) on the ectodomain of the CAR recognizes tumor-associated antigens on the surface of tumor cells, binds to them, and initiates a cascade of cytotoxic signaling, that leads to tumor lysis.
The ectodomain is linked to the intracellular domains by a hinge/transmembrane region, commonly derived from CD8 or IgG4. The intracellular portion is the signaling domain. In the first generation of CARs, this included only the CD3 signaling
domain, which lacked a proliferation profile. The second- and third-generation CARs now include 1 (second generation) or 2 (third generation) costimulatory domains that are typically 4-1BB, CD28, and/or OX-40 to promote efficient T-cell signaling and persistence. Fourth-generation CARs (TRUCKs), which further affect the tumor microenvironment to induce cytokine production after the CAR recognizes the target antigens, and fifth-generation CARs are being developed to further improve CAR efficiency and longevity.
On the other hand, bispecific antibodies use patients unengineered T cells. The off-the-shelf antibody is designed so that 1 end binds to a multiple myeloma cell and the other end binds to a killer T cell. The first bispecific antibody for multiple myeloma was developed with an ScFV that attached to the tumor antigen and another that attached to CD3 of the T cell receptor complex of the T cell with a linker. The halflife was short and continuous infusion was required. Since then, bispecific antibodies are manufactured with an Fc segment that increases the half-life so that the agent can be administered weekly or less frequently; this is the treatment of choice in ongoing clinical trials. New agents in development include trispecific antibodies that may have a costimulatory protein or target dual myeloma antigens or antibodies that engage natural killer cells.
There are several tumor antigens being investigated as suitable targets for CAR T-cell and T-cell redirected therapies, such as CD38, CD138, SLAMF7, CD19, and more. However, the most widely studied target for both CAR T-cell therapies and for bispecific antibody therapies is B-cell maturation antigen (BCMA).
BCMA is a cell surface receptor in the tumor necrosis factor receptor superfamily member 17 (TNFRSF17). It is deemed an ideal antigenic target because it is expressed specifically on normal and malignant plasma cells but not on hematopoietic stem cells, and has higher expression on myeloma cells than normal plasma cells. It plays a key role in B-cell maturation and differentiation and promotes myeloma cell growth by binding to its ligands BAFF and APRIL. Expression of BCMA increases with progression from MGUS to advanced myeloma.
Based on encouraging results from the first major global multicenter phase 1 anti- BCMA CAR T study (NCT02658929) conducted in relapsed or refractory multiple myeloma1, investigators initiated the pivotal phase 2 KarMMa trial (NCT03361748).2 The results of this trial were updated at the 18th International Myeloma Workshop (IMW) held in Vienna, Austria, in September.3
Idecabtagene vicleucel (ide-cel; Abecma), formally bb2121, is an anti-BCMA second-generation CAR construct with a 41BB costimulatory domain. Among 128 patients enrolled in the KarMMa study, 84% were triple-class refractory. At a median follow-up of 24.8 months, the overall response rate (ORR) was 73%, with complete response (CR) or stringent CR (sCR) reported in 33% of responders. Minimal residual disease (MRD) was negative in 79% of complete responders. Further, responses were attained at a median of 1 month (range, 0.5-8.8) and the median duration of response (DOR) was 10.9 months.
The median progression-free survival (PFS) was 8.6 months and median overall survival (OS) was 24.8 months. DOR and PFS were improved in the higher-dose ranges and in complete responders. Similar degrees of responses were observed in all subgroups, including Revised International Staging System for multiple myeloma III criteria, extramedullary disease, and high tumor burden. In terms of adverse effects (AEs), cytopenias were observed in 97% of patients. Grade 3/4 neutropenia was seen in 89% of patients, grade 3/4 thrombocytopenia was seen in 52%, and grade 3/4 infections in 23%. Cytokine release syndrome (CRS) was seen in 84% of patients: 78% at grade 1/2, 6% at grade 3 or higher. CRS occurred at a median onset of 2 days and median duration was 5 days. Neurotoxicity was reported in 18% of patients, 4% of whom reported the AE as grade 3 or higher. Results of the study led to FDA approval of the first, commercially approved CAR T-cell product in March.
CARTITUDE-1 was a phase 1b/2 study (NCT03548207)4 that used a different CAR T product, ciltacabtagene autolecleucel (cilta-cel). Updated findings were presented from Usmani et al5 at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and at IMW from Jagannath et al.6
Cilta-cel is a lentiviral vector-based anti-BCMA construct with a 41BB costimulatory domain. The BCMA-catching domain targets 2 different epitopes simultaneously, increasing the binding affinity, and is the same CAR construct as in the Chinese trial LEGEND-2 (NCT03090659).
In CARTITUDE-1, 97 patients with a median of 6 prior lines of therapy were enrolled. At baseline, 88% were triple-class refractory and 99% were refractory to their last line of therapy. At a median follow-up of 18 months, the ORR was 98% for all patients and included an sCR rate of 80%. Responses were attained at a median of 1 month and deepened over time. The median DOR was 21.8 months overall (95% CI, 21.8-not estimable) and was not reached in patients with sCR. MRD negativity was achieved in 92.0% of evaluable patients.
The 18-month PFS rate was 66% (95% CI, 54.9%-75.0%) and the 18-month OS rate was 80.9% (95% CI, 71.4%-87.6%). These results far surpass outcomes with other nonT-cell mediated novel agent therapies in triple-class refractory patients.
In terms of safety, cytopenias were universal and 92 of 97 patients experienced any-grade CRS; 95% were grade 1/2 and had a median time of onset of 7 days and duration of 4 days. All-grade neurotoxicity was reported for 21% of patients, 10% of whom had neurotoxicity of grade 3 or higher. Although most neurotoxic events occurred in the setting of CRS, 12 patients had late neurotoxicity, 6 of whom resolved, 1 had ongoing neurotoxicity, and 1 died because of neurotoxicity. There were 21 deaths on study: 2 occurred in fewer than 100 days, 10 deaths were because of disease progression, and 6 were because of treatmentrelated AEs. Late recovery (greater than 1 month) of grade 3/4 cytopenias from first onset was seen in 10% of patients with neutropenia and 26% of those with thrombocytopenia.
At the American Society of Hematology (ASH) Annual Meeting 2020, Shah et al7 presented an analysis that compared efficacy outcomes seen in the KarMMa trial with those reported from the MAMMOTH study,8 which was a retrospective observational study of conventional care regimens in patients with triple-class refractory multiple myeloma.
The MAMMOTH study, which has been used in other comparative studies, has been a benchmark for investigators to compare therapeutic maneuvers in patients with triple-class exposed relapsed or refractory multiple myeloma who have received various standard-of-care therapies. The analysis applied matching-adjusted indirect comparisons to assess the efficacy of ide-cel and conventional care and showed that, in a matched population, ide-cel treatment was associated with a significantly higher ORR, PFS, and OS than conventional care.
Cilta-cel was similarly compared with conventional treatment in the MAMMOTH study and was presented by Costa et al at ASCO 2021.9 The MAMMOTH data set was used to identify patients with multiple myeloma refractory to anti- CD38 monoclonal antibodies who would meet eligibility for CARTITUDE-1 and who received conventional therapy. The intention-to-treat population (ITT) in CARTITUDE-1 was defined as patients who underwent apheresis, and a modified ITT population was defined as subset of patients who received cilta-cel at the recommended phase 2 dose (RP2D).
ORR, PFS, and OS for both the ITT population and modified ITT population in CARTITUDE-1 vs matching MAMMOTH cohorts were found to be superior. Specifically, the ORR in the ITT cohort was higher in CARTITUDE-1 compared with the MAMMOTH counterpart (84% vs 28%). Patients in the CARTITUDE-1 ITT cohort vs MAMMOTH cohort had improved PFS and OS rates at 12 months, 73% vs 12% and 83% vs 39%, respectively. Comparing the modified ITT cohorts, patients in CARTITUDE-1 had superior ORR (96% vs 30%), 12-month PFS rate (79% vs 15%) and 12-month OS rate (88% vs 41%).
Therefore, in patients with relapsed or refractory multiple myeloma beyond therapy with immunomodulatory drugs, proteasome inhibitor, and anti-CD38 monoclonal antibody, treatment with ide-cel or cilta-cel is associated with higher response rate and superior PFS and OS when compared with conventional treatment.
Other CAR T trials were reported at ASH 2020 and are being studied in various phase 1/2 trials. Research is directed at improving the efficacy and persistence of CAR products, which vary by source of product (autologous vs allogeneic CAR T cells), choice of vector (lentiviral, retroviral, or nonviral DNA transposon technology), use of humanized ScFv to prevent immunogenicity, CD4/CD8 ratio controlled to enrich for central memory phenotype to improve longevity of CAR T cells, dual target constructs to prevent relapses because of antigen escape, CARs against non-BCMA targets to treat BCMA negative relapses, and more.
Bispecific antibodies are in earlier stages of development than CAR T. The majority of anti bodies target BCMA, although there are some targeting antigens other than BCMA that have great potential in patients who have relapsed post BCMA-targeted therapies with BCMAnegative plasma cells.
Teclistamab is an anti-BCMA/anti-CD3 bispecific antibody with intravenous and subcutaneous formulations. Results of the MajesTEC-1 study (NCT03145181) were published in Lancet.10,11 Investigators treated 157 patients with a median of 6 prior lines of therapy, of whom 82% were triple-class refractory, 90% were refractory to their last regimen, and 85% were previously transplanted were enrolled to a dose escalation/ expansion study. A total of 40 patients received the RP2D of 1500 g/kg. At RP2D, the median time to response was 1 month and median time to CR was 3 months.
At a median follow-up of 7.2 months, median DOR was not reached (7.2-not reached). The ORR was 65% in the RP2D group, 58% had a very good partial response (VGPR) or better, and 40% had a CR or better. Importantly, the majority of patients in CR were MRD negative at 10-6. Among responders, 85% were alive and progression free at follow-up. The most common AEs of any grade were CRS, all grade 1 or 2 (70%), and neutropenia (65%). Grade 3 or 4 AEs occurred in 80% of patients, with the most common being neutropenia (40%), anemia (28%), and thrombocytopenia (20%). Infections occurred in 45% of patients and were grade 3 or higher in 23%.
Talquetamab is an anti-GPRC5D/CD3 first-in-class duo antibody. Results from the phase 1 MonumenTAL-1 trial (NCT04634552) were presented by Chari et al at ASH 202012 and updated at IMW by van de Donk et al.13
GPRC is highly expressed in poor-risk myeloma, and in hair follicles. In the MonumenTAL-1 trial, 174 patients with a median of 6 prior lines of therapy were enrolled, 102 to the intravenous arm and 72 to the subcutaneous formulation arm, in dose escalation and expansion cohorts. At baseline 71% of patients were triple-class refractory and 86% were refractory to last line of therapy; 21% of patients had received prior BCMA-targeted therapies.
The ORR was 70% at the RP2D, and 50% of responders had a VGPR or better, with a median time to first confirmed response of 1 month. Responses were durable and deepened over time, with 81% of responders continuing on treatment after a median follow-up of 6.3 months. CRS was reported in 79% of patients; 4% had CRS of grade 3/4. Median time to onset of CRS was a day after subcutaneous dose, and the duration was 2 days. Neurotoxicity was reported in 7% of patients (grade 1/2) and was mostly in the context of CRS. Grade 1/2 skin-related AEs were seen in 75% of patients and nail-related AEs in 18%. Dysgeusia was reported in 57% of patients. A phase 2 expansion study (MonumenTAL-2) is recruiting. Patients will receive talquetamab at the RP2D.
Various other bispecific antibodies are in clinical trials, including Regeneron 5458, another anti-BCMA/anti-CD3 bispecific antibody with very encouraging results reported at ASH last year.14 The ORR was 63% and responses were achieved by 1 month. The median DOR was 6 months, and among responders with more than 6 months of follow-up, 83% had ongoing responses for up to 13 months and 74% of responders remained on treatment. TNB-383B is a fully human triple-chain BCMA CD3 bispecific antibody with a unique anti-CD3 moiety for target lysis with minimal cytokine release and 2 anti-BCMA moieties. It is administered intravenously every 3 weeks without step-up dosing. Data for 58 patients from the ongoing first-in-human study were presented at ASH 2020.15 Safety data were comparable with results of other studies.
Cevostamab is another nonBCMA bispecific antibody. The target antigen is FcRH5, which is found on nave and memory B cells and plasma cells. The anti-FcRH5/anti-CD3 is administered intravenously every 3 weeks, and data were presented at ASH 2020 last year as well.16 Finally, CC-93269, a bispecific antibody with 1 CD3 and 2 BCMA binding sites, shows encouraging early data as well.
Future directions for bispecific antibodies include understanding resistance mechanisms, studying them in combination with various agents, and understanding sequencing strategies.
Because myeloma is marked by clonal heterogeneity, combinations of drugs with different mechanisms of action and nonoverlapping toxicities are frequently used with success. With the arrival of this new era of powerful immunotherapeutic tools such as CAR T and T-cell redirective agents, a sound understanding of their optimal use is key to maximizing their potential.
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Therapeutic Frontiers for Relapsed/Refractory Multiple Myeloma Expand With CAR T and Bispecific Antibodies - OncLive
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Genetic Engineering Products | Boundless Microbiology
Posted: at 9:44 pm
Overview of Biotechnology
Biotechnology is the use of biological techniques and engineered organisms to make products or plants and animals that have desired traits.
Describe the historical development of biotechnology
Biotechnology: Brewing (fermentation of beer) was an early application of biotechnology.
People have used biotechnology processes, such as selectively breeding animals and fermentation, for thousands of years. Late 19th and early 20th century discoveries of how microorganisms carry out commercially useful processes and how they cause disease led to the commercial production of vaccines and antibiotics. Improved methods for animal breeding have also resulted from these efforts. Scientists in the San Francisco Bay Area took a giant step forward with the discovery and development of recombinant DNA techniques in the 1970s. The field of biotechnology continues to accelerate with new discoveries and new applications expected to benefit the economy throughout the 21st century.
In its broadest definition, biotechnology is the application of biological techniques and engineered organisms to make products or modify plants and animals to carry desired traits. This definition also extends to the use of various human cells and other body parts to produce desirable products. Bioindustry refers to the cluster of companies that produce engineered biological products and their supporting businesses. Biotechnology refers to the use of the biological sciences (such as gene manipulation), often in combination with other sciences (such as materials sciences, nanotechnology, and computer software), to discover, evaluate and develop products for bioindustry. Biotechnology products have made it easier to detect and diagnose illnesses. Many of these new techniques are easier to use and some, such as pregnancy testing, can even be used at home. More than 400 clinical diagnostic devices using biotechnology products are in use today. The most important are screening techniques to protect the blood supply against contamination by AIDS and the hepatitis B and C viruses.
Genetic engineering means the manipulation of organisms to make useful products and it has broad applications.
Describe the major applications of genetic engineering
Genetic engineering, also called genetic modification, is the direct manipulation of an organisms genome using biotechnology.
New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest, using molecular-cloning methods to generate a DNA sequence; or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or knocked out, using a nuclease.
Genetically manipulated mice: Laboratory mice are genetically manipulated by deleting a gene for use in biomedical research.
Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations. Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and microorganisms.
Genetic engineering has produced a variety of drugs and hormones for medical use. For example, one of its earliest uses in pharmaceuticals was gene splicing to manufacture large amounts of insulin, made using cells of E. coli bacteria. Interferon, which is used to eliminate certain viruses and kill cancer cells, also is a product of genetic engineering, as are tissue plasminogen activator and urokinase, which are used to dissolve blood clots.
Another byproduct is a type of human growth hormone; its used to treat dwarfism and is produced through genetically-engineered bacteria and yeasts. The evolving field of gene therapy involves manipulating human genes to treat or cure genetic diseases and disorders. Modified plasmids or viruses often are the messengers to deliver genetic material to the bodys cells, resulting in the production of substances that should correct the illness. Sometimes cells are genetically altered inside the body; other times scientists modify them in the laboratory and return them to the patients body.
Since the 1990s, gene therapy has been used in clinical trials to treat diseases and conditions such as AIDS, cystic fibrosis, cancer, and high cholesterol. Drawbacks of gene therapy are that sometimes the persons immune system destroys the cells that have been genetically altered, and also that it is hard to get the genetic material into enough cells to have the desired effect.
Many practical applications of recombinant DNA are found in human and veterinary medicine, in agriculture, and in bioengineering.
Describe the advances made possible by recombinant DNA technology
Recombinant DNA technology is the latest biochemical analysis that came about to satisfy the need for specific DNA segments. In this process, surrounding DNA from an existing cell is clipped in the desired amount of segments so that it can be copied millions of times.
Construction of recombinant DNA: A foreign DNA fragment is inserted into a plasmid vector. In this example, the gene indicated by the white color is inactivated upon insertion of the foreign DNA fragment.
Recombinant DNA technology engineers microbial cells for producing foreign proteins, and its success solely depends on the precise reading of equivalent genes made with the help of bacterial cell machinery. This process has been responsible for fueling many advances related to modern molecular biology. The last two decades of cloned-DNA sequence studies have revealed detailed knowledge about gene structure as well as its organization. It has provided hints to regulatory pathways with the aid of which gene expression in myriad cell types is controlled by the cells, especially in those organisms having body plan with basic vertebrae structure.
Recombinant DNA technology, apart from being an important tool of scientific research, has also played a vital role in the diagnosis and treatment of various diseases, especially those belonging to genetic disorders.
Some of the recent advances made possible by recombinant DNA technology are:
1. Isolating proteins in large quantities: many recombinant products are now available, including follicle stimulating hormone (FSH), Follistim AQ vial, growth hormone, insulin and some other proteins.
2. Making possible mutation identification: due to this technology, people can be easily tested for mutated protein presence that can lead to breast cancer, neurofibromatosis, and retinoblastoma.
3. Hereditary diseases carrier diagnosis: tests now available to determine if a person is carrying the gene for cystic fibrosis, the Tay-Sachs diseases, Huntingtons disease or Duchenne muscular dystrophy.
4. Gene transfer from one organism to other: the advanced gene therapy can benefit people with cystic fibrosis, vascular disease, rheumatoid arthritis and specific types of cancers.
Bacterial genetics can be manipulated to allow for mammalian gene expression systems established in bacteria.
Describe the sequence of events in a genetically engineered expression system
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins and are produced after the process of translation. An expression system that is categorized as a genetic engineering product is a system specifically designed for the production of a gene product of choice. This is normally a protein, although may also be RNA, such as tRNA or a ribozyme.
The genetically engineered expression system contains the appropriate DNA sequence for the gene of choice which is engineered into a plasmid that is introduced into a bacteria host. The molecular machinery that is required to transcribe the DNA is derived from the innate and naturally occurring machinery in the host. The DNA is then transcribed into mRNA and then translated into protein products.
In a genetically engineered system, this entire process of gene expression may be induced depending on the plasmid used. In the broadest sense, mammalian gene expression includes every living cell but the term is more normally used to refer to expression as a laboratory tool. An expression system is therefore often artificial in some manner. Viruses and bacteria are an excellent example of expression systems.
The oldest and most widely used expression systems are cell-based. Expression is often done to a very high level and therefore referred to as overexpression. There are many ways to introduce foreign DNA to a cell for expression, and there are many different host cells which may be used for expression. Each expression system also has distinct advantages and liabilities.
Expression systems are normally referred to by the host and the DNA source or the delivery mechanism for the genetic material. For example, common bacterial hosts are E.coli and B. subtilis. With E. coli, DNA is normally introduced in a plasmid expression vector. The techniques for overexpression in E. coli work by increasing the number of copies of the gene or increasing the binding strength of the promoter region so as to assist transcription.
Bacterial Flora: E. coli is one of the most popular hosts for artificial gene expression.
Genetic engineering enables scientists to create plants, animals, and microorganisms by manipulating genes.
Explain the advantages and disadvantages of producing genetically engineered proteins in bacteria
The first successful products of genetic engineering were protein drugs like insulin, which is used to treat diabetes, and growth hormone somatotropin. These proteins are made in large quantities by genetically engineered bacteria or yeast in large bioreactors. Some drugs are also made in transgenic plants, such as tobacco. Other human proteins that are used as drugs require biological modifications that only the cells of mammals, such as cows, goats, and sheep, can provide. For these drugs, production in transgenic animals is a good option. Using farm animals for drug production has many advantages because they are reproducible, have flexible production, are easily maintained, and have a great delivery method (e.g. milk).
Synthetic Insulin: human insulin produced by recombinant DNA technology.
Recombinant DNA technology not only allows therapeutic proteins to be produced on a large scale but using the same methodology protein molecules may be purposefully engineered. Genetic modifications introduced to a protein have many advantages over chemical modifications. Genetically engineered entities are biocompatible and biodegradable. The changes are introduced in 100% of the molecules with the exclusion of rare errors in gene transcription or translation. The preparations do not contain residual amounts of harsh chemicals used in the conjugation process. Bacterial expression systems, due to their simplicity, are often not able to produce a recombinant human protein identical to the naturally occurring wild type. Bacteria did not develop sophisticated mechanisms for performing post-translational modifications that are present in higher organisms. As a consequence, an increasing number of protein therapeutics is expressed in mammalian cells. However the low cost and simplicity of cultivating bacteria is an unbeatable advantage over any other expression system and therefore E. coli is always a preferable choice both on a lab scale and in industry.
Many mammalian proteins are produced by genetic engineering. These include, in particular, an assortment of hormones and proteins for blood clotting and other blood processes. For example, tissue plasminogen activator (TPA) is a blood protein that scavenges and dissolves blood clots that may form in the nal stages of the healing process. TPA is primarily used in heart patients or others suffering from poor circulation to prevent the development of clots that can be life-threatening. Heart disease is a leading cause of death in many developed countries, especially in the United States, so microbially produced TPA is in high demand. In contrast to TPA, the blood clotting factors VII, VIII, and IX are critically important for the formation of blood clots. Hemophiliacs suffer from a deciency of one or more clotting factors and can therefore be treated with microbially produced clotting factors. In the past hemophiliacs have been treated with clotting factor extracts from pooled human blood, some of which was contaminated with viruses such as HIV and hepatitis C, putting hemophiliacs at high risk for contracting these diseases. Recombinant clotting factors have eliminated this problem.
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7.23B: Applications of Genetic Engineering – Biology …
Posted: at 9:44 pm
Genetic engineering means the manipulation of organisms to make useful products and it has broad applications.
Genetic engineering, also called genetic modification, is the direct manipulation of an organisms genome using biotechnology.
New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest, using molecular-cloning methods to generate a DNA sequence; or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or knocked out, using a nuclease.
Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations. Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and microorganisms.
Genetic engineering has produced a variety of drugs and hormones for medical use. For example, one of its earliest uses in pharmaceuticals was gene splicing to manufacture large amounts of insulin, made using cells of E. coli bacteria. Interferon, which is used to eliminate certain viruses and kill cancer cells, also is a product of genetic engineering, as are tissue plasminogen activator and urokinase, which are used to dissolve blood clots.
Another byproduct is a type of human growth hormone; its used to treat dwarfism and is produced through genetically-engineered bacteria and yeasts. The evolving field of gene therapy involves manipulating human genes to treat or cure genetic diseases and disorders. Modified plasmids or viruses often are the messengers to deliver genetic material to the bodys cells, resulting in the production of substances that should correct the illness. Sometimes cells are genetically altered inside the body; other times scientists modify them in the laboratory and return them to the patients body.
Since the 1990s, gene therapy has been used in clinical trials to treat diseases and conditions such as AIDS, cystic fibrosis, cancer, and high cholesterol. Drawbacks of gene therapy are that sometimes the persons immune system destroys the cells that have been genetically altered, and also that it is hard to get the genetic material into enough cells to have the desired effect.
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Arctic Apples: A fresh new take on genetic engineering …
Posted: at 9:44 pm
by Allison Bakerfigures by Lillian Horin
The Arctic apple is the juiciest newcomer to produce aisles. It has the special ability to resist browning after being cut (Figure 1), which protects its flavor and nutritional value. Browning also contributes to food waste by causing unappealing bruising on perfectly edible apples. Food waste, especially for fruits and vegetables, is a major problem worldwide; nearly half of the produce thats grown in the United States is thrown away, and the UK supermarket Tesco estimates that consumer behavior significantly contributes to the 40% of its apples that are wasted. Therefore, Arctic apples not only make convenient snacks, but they also might be able to mitigate a major source of food waste.
While a non-browning apple sounds great, how exactly was this achieved? Arctic apples are genetically engineered (GE) to prevent browning. This means that the genetic material that dictates how the apple tree grows and develops was altered using biotechnology tools. But before learning about the modern science used to make Arctic apples, lets explore how traditional apple varieties are grown.
Harvesting tasty apples is more complicated than simply planting a seed in the ground and waiting for a tree to grow. In particular, its difficult to predict what an apple grown from a seed will look and taste like because each seed contains a combination of genetic material from its parents. But farmers can reliably grow orchards of tasty apples by using an ancient technique called grafting. After a tree that produces a desirable apple is chosen, cuttings of that original tree are grafted, or fused, onto the already-established roots of a donor tree, called rootstock. The cuttings then grow into a full-sized tree that contains the exact same genetic material as the original tree. As a result, each tree of a specific apple variety is a cloned descendant of the original tree, and thus produce very similar apples.
New apple varieties emerge when genetic changes are allowed to occur. Traditionally, new apples are produced by cross-breeding existing apple varieties. This reshuffles the genetic makeup of seeds, which are then planted to see if they grow into trees that produce delicious new apples. On the other hand, Arctic apples are created by making a targeted change to the genetic material of an existing variety (more on this later). The advantage of using genetic engineering over traditional breeding methods is that scientists can efficiently make precise improvements to already-beloved apple varietiesin contrast, traditional cross-breeding is much more random and difficult to control.
Insight into the molecular causes of apple browning guided the genetic alteration that made Arctic apples. Apples naturally contain chemicals known as polyphenols that can react with oxygen in the air to cause browning. This reaction wont occur, however, without the help of polyphenol oxidase (PPO) enzymes, which bring polyphenols and oxygen together in just the right way. PPO enzymes and polyphenols are normally separated into different compartments in apple cells, which is why the inside of a fresh apple is white or slightly yellow-green in color. But these structures are broken when the fruit is cut or crushed, allowing PPOs to interact with polyphenols and oxygen to drive the browning reaction(Figure 2). This process occurs in all apples, but some varieties are less susceptible than others due to factors like lower amounts of PPOs or polyphenols. Common household tricks can also delay browning by a few hours by interfering with the PPO reaction, but no method prevents it completely or indefinitely. Knowing that PPOs were responsible for browning, researchers thought about blocking the production of these enzymes with genetic tools to create non-browning apples.
Genetic material is stored in our DNA and divided into functional units called genes. The genes are read by copying the DNA sequence into a related molecule called RNA. The RNA copy functions as a blueprint that instructs the cell how to build the product for that gene, which is called a protein. The production of PPO enzymes, therefore, can be blocked by simply removing their RNA blueprints. To do so, researchers used a tool from molecular biology called RNA interference (RNAi). RNAi is a natural biological process that recognizes and destroys specific RNA structures. Biologists can use RNAi to lower PPO levels by introducing RNA sequences that cause the degradation of PPO RNA. Using this technique, researchers developed an anti-PPO gene that makes anti-PPO RNA, which destroys the PPO RNA before it can be used to make PPO enzymes.
Once scientists created the anti-PPO gene, they needed to safely introduce it into the apple genome. To make a variety called the Arctic Golden, researchers began with Golden Delicious apple buds and inserted an engineered piece of genetic material called a transgene that contained the anti-PPO gene. After confirming that the plant received the transgene, the saplings were then allowed to grow into mature trees, one of which produced the apple that is now known as the Arctic Golden.
After over a decade of research, regulatory agencies in the United States and Canada like the FDA and USDA recently approved Arctic apples for human consumption. Accumulated evidence shows that Arctic apple trees and fruit are no different from their traditional counterparts in terms of agricultural and nutritional characteristics. On the molecular level, the transgene genetic material present in Arctic apples is quickly degraded by your digestive system to the point where its indistinguishable from that found in traditional apples. The only new protein in Arctic apple treesa protein called NPTII thats used to confirm that the genetic engineering was successfulwas not only undetectable in their apples, but it has also been evaluated and deemed nontoxic and non-allergenic by the FDA.
Yet some anti-GMO groups continue to protest the approval of Arctic apples, arguing that unforeseen consequences of the genetic alteration could impact safety. Its true that its impossible to predict and disprove every possible consequence of a genetic change. But a recent review by the National Academies of Science that covers decades of published research found no convincing evidence that GE crops have negatively impacted human health or the environment. While its important to rigorously test all new crops that are developed, GE crops should not be considered inherently more dangerous than their traditionally-bred relatives.
So whats next for the Arctic apple? It takes several years for new apple trees to grow and literally bear fruit, so itll take time for non-browning apples to expand to supermarkets throughout the US. Currently, Arctic Goldens are only available in bags of pre-sliced apples in select US cities, but Arctic versions of Granny Smith and Fuji apples have received USDA approval, and Arctic Galas are in development. If commercially successful, non-browning apples could help to combat rampant food waste one slice at a time.
Allison Baker is a second-year Ph.D. student in Biological and Biomedical Sciences at Harvard University.
Cover image credit:Okanagan Specialty Fruits Inc.
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Have biotech advocates lost Soylent as an ally in the food industry? – AGDAILY
Posted: at 9:44 pm
Few food companies over the past decade have voluntarily promoted the use of genetic engineering on their labels. After all, organizations such as the Non-GMO Project have profited heavily by demonizing the use of biotechnology in agriculture and food. But one company that stood above the fray and celebrated this sustainable science was Soylent.
The California-based company specializes in ready-to-drink meals that are built around soy protein a 14-ounce bottle clocks in at about 400 calories and is available in a wide variety of flavors, from vanilla and strawberry to chocolate mint and cafe mocha. Ive been a customer for several years, drawn not only by the taste and convenience of their product but also by the fact that Soylent had long proudly marketed a pro-GMO stanceand emblazoned their bottles with a Produced with genetic engineering statement.
That means a lot to someone like me who sees the adoption of science and sustainable technologies vital to advancing our food system, to overhauling our use of crop inputs, and to increasing efficiencies along the food chain. The use of genetic engineering in food is a viable and exciting way forward for our industry and reckless opponents of this science like the Non-GMO Project should be damned.
So, its been with some concern that my last several shipments of Soylent drinks have come in new packaging that has removed the previous mention of genetic engineering. The pro-GMO approach had been instrumental to their marketing, and it wasnt long ago that then-CEO Bryan Crowley observed that the public was becoming more accepting of genetic engineering, and that the the pendulum is swinging in favor of the science.
But to look at Soylent now, under CEO Demir Vangelov, all mentions of genetic engineering or GMOs have been scrubbed from their website the companys blog post that was titled Proudly Made With GMOs has been taken down, as has the Soylent Help Center page titled Why is Soylent made with GMOs.
Some new packaging incorporates the U.S. Food and Drug Administrations bioengineered logo, albeit its so small as to be virtually unreadable (especially the actual bioengineered wording on the logo). Yet that step feels forced in comparison to the wording theyve voluntarily had on their products in the past. And, unfortunately, Soylent hasnt used the FDAs logo on all of its varieties this year.
The company still claims to be leading the charge in innovation, but their actions regarding biotechnology dont bear that out.
Communities have been taking notice of this unfortunate labeling change, too. A Reddit thread from early 2021 pointed out the removal of the wording, with most of the more than 100 comments lamenting the decision and criticizing Soylent.
One poster emphatically said: Give me my GMOs!/You know whos against GMOs? Anti-vaxers, flat-earthers, qannon crackheads, and anti-science idiots.
Other comments further show support for science, such as: GMO is class though, its literally super food, and GMO foods are good stuff, theyve removed carcinogens from potatoes. Made crops more resilient to different climates. They use less pesticide, drought resistant.
The overarching feeling from the Reddit thread is that Soylent is wilting away from sound science and dumbing down their approach in order to make a profit even if the company still uses genetically engineered soybeans without disclosing it as prominently.
I reached out to Soylent multiple times through social media and their website, as well as via their marketing department, to get an explanation or more insight into what was going on, but like on the companys platforms, GMOs seem to be a topic that no one there is willing to discuss.
This should be a concern. Generation Z (those born in the mid-to-late 90s) has shown itself to be more open to food technologies than any other generation, which gives this up-and-coming consumer base a lot of power in the food market moving forward. Additionally, many measures show that the fear and opposition to GMOs have been waning, and public sentiment has moved on to topics such as lab-grown meat and farmings role in the climate debate.
That makes the timing of Soylents shift all that much more perplexing. Soylent weathered the worst of the social storm around GMOs through the 2010s, yet now, theyre actively regressing the gains and acceptance that had emerged.
After all, even Crowley, the former CEO, said that its not about being pro-GMO, its about being pro-science.
And when companies such as General Mills or youth organizations such as the Girl Scouts can embrace biotechnology as the most viable path forward for a growing population, its particularly stinging that Soylent shies from its roots and fecklessly gives fresh ammunition to opponents of food tech.
Ryan Tipps is the managing editor for AGDAILY. He has covered farming since 2011, and his writing has been honored by state- and national-level agricultural organizations.
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Studying the unintended effects of gene editing in tomatoes – hortidaily.com
Posted: at 9:44 pm
Yi Li, professor of plant science in the College of Agriculture, Health, and Natural Resources is working on a new $500,000 Biotechnology Risk Assessment Research Grant (BRAG) from the USDA/NIFA to study a genetic editing technique in tomato plants.
Genetically engineered organisms are becoming increasingly popular given their potential applications to improve the food supply. Gene editing allows scientists to manipulate an organisms DNA, leading to produce that stays fresher longer, resists pests and viruses, or has higher nutritional content.
One common method of gene editing is manipulating DNA methylation. DNA methylation is the process by which methyl groups are added to a DNA molecule. This changes the activity of that DNA segment without changing the DNA itself. Methylation can suppress or promote the expression of certain genes and the proteins they code for.
Unstudied side effectsThis promising gene-editing technique could improve crops on a large scale. However, the potential unintended side effects of this process are not well-studied, hindering its potential agricultural applications.
Li will specifically look at CRISPR/dCas-mediated DNA methylation in tomatoes. Research on this technique has shown there are some off-target effects, or methylation changes to parts of the genome scientists were not intentionally changing, but no one has yet characterized what these effects are, creating a significant knowledge gap Li is now looking to fill.
Li will compare this methylation technique to genetic transformation, another gene-editing technique. Genetic transformation differs from DNA methylation because it involves introducing foreign DNA into the plants genome, rather than working on changing the expression of its own. Li will compare these two gene-editing techniques to more conventional growing techniques without gene editing.
Li will examine the DNA methylation, RNA sequences, fruit quality, and other observable characteristics for each method. This work will directly address the BRAG Programs priority to gain information about the types and frequencies of nucleic acid changes various genetic engineering techniques introduce into important crops, like tomatoes.
This work will also support the BRAG program goal of providing regulatory agencies with the knowledge to make scientifically informed decisions regarding genetically engineered organisms to protect consumers and the environment. This aspect of the project will be largely carried out by co-principal investigator, Stacey Stearns. Stearns is a communications specialist at UConn Extension.
The knowledge generated from this study will aid plant breeders practicing DNA methylation editing in crops and facilitate the policy- and decision-making process at federal regulatory agencies, Li says.
Lis project includes a public education component. Li and his team will create and share articles, websites, videos, and presentations with the general public.
This outreach will help the public better understand gene-editing technology and its applications for agriculture. Education about genetic engineering can help dispel misinformation and misunderstandings about gene editing.
For more information:University of Connecticutwww.uconn.edu
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Life As We Made It review: Should we go all in on gene-editing tech? – New Scientist
Posted: at 9:44 pm
By Gege Li
Some people dislike the idea of eating genetically modified foods
Tony Savino/Corbis via Getty Images
Book
Life As We Made It
Beth Shapiro
LOOK around you, and the results of humanitys time on Earth are plain to see. Our species has been changing and refining the environment for generations. Landscapes and habitats that we take for granted as natural would look and behave very differently if humans hadnt come on the scene and thats before you factor in our effects on other species.
In Life As We Made It, Beth Shapiro, a professor of ecology and evolutionary biology at the University of California, Santa Cruz, explores the ways that humans have transformed the world around us. In doing so, we have taken the reins of not only our own evolution, but also that of many other species, for better or worse.
Shapiro travels back in time to when our ancestors first learned how to break the rules of nature and follows our environmental tinkering to the present day, where the rise of new biotechnologies is giving us more power and influence than ever before.
The first part of the book, The Way It Is, looks at how we began figuring out ways to change our environment rather than letting it change us. At first, this was unintentional. But 50,000 years ago, we made a pivotal transition from existing alongside other species to becoming apex predators, then domesticators, farmers and innovators. This was an important shift because it let us direct our own evolutionary path. It meant that those who may not have survived previously could live long enough to pass on their genes.
This, says Shapiro, is how we became different, unquestionably, from every other species that lives or has ever lived on Earth. This is what it means to be human.
She draws on a variety of influences to investigate this idea, from our ancestors interactions with other hominins, such as Neanderthals, and mass extinctions throughout history that were probably caused at least partly by humans spreading across the planet, overturning ecosystems as we went.
The second part of the book, The Way It Could Be, casts a spotlight on arguably the most significant point in human history so far: the advent of technologies that let us edit genomes directly. This has allowed us to engineer desired traits into organisms that benefit us, and has opened up unprecedented realms of possibility to reroute evolution as we please. With such methods, we have the power to edit out diseases, save endangered species from extinction, develop more sustainable materials, remove pollutants from oceans and much more besides. With synthetic biology, we no longer have to remain within the bounds of what we can imagine, writes Shapiro.
We probably shouldnt have free rein with new gene-editing technology with it comes responsibility
We probably shouldnt allow ourselves free rein with this new technology with it comes the responsibility to regulate the processes and resulting creations, and to decide when to use it, and whether it should be done at all.
On this last point, Shapiro argues that decades of misinformation and sensationalism around genetically modified organisms, as well as fears of whether we should be playing God, have led to public mistrust and unease. She calls this a knee-jerk yuck factor and says it is a significant barrier to realising the full potential of genetic engineering.
Shapiro makes a strong case that, given the pressing issues we face today a growing global population, climate change and biodiversity loss we will increasingly need to look to these tools if our species and others are to survive and thrive. We cant both maintain the comfortable randomness of evolution and at the same time propel our world toward a defined future, she says.
While that is an undoubtedly important conversation, this is where Life As We Made It starts to stray slightly from its aim of exploring human innovation. For me, the book is most revealing when it considers how we have changed nature through the lens of our past interactions with other species, sometimes simply because we worked out how to breed different animals and plants to our advantage.
Nonetheless, the book provides a detailed exploration of some of the most influential technologies of our time. It also offers a tantalising glimpse of what might be in store in the future, when humanity starts to mix things up all over again.
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On announces CleanCloud – turning carbon emissions into running shoes in cooperation with LanzaTech and Borealis – Yahoo Finance
Posted: at 9:44 pm
Swiss sports brand On leads supply chain coalition to reshape carbon waste into running shoes
Main Facts:
- On announces CleanCloud - a sustainability initiative using carbon emissions to create foam for running shoes.
- On is moving away from petroleum-based resources and is reshaping carbon waste into EVA foam.
- On is the first company in the footwear industry to explore carbon emissions as a primary raw material for a shoe bottom unit.
- On is partnering with LanzaTech and Borealis, two of the most innovative companies in biochemicals, process, and polymer innovation.
ZURICH, Nov. 5, 2021 /PRNewswire/ -- Swiss sports brand On today announces a move away from petroleum-based resources by creating a new foam material called CleanCloud, made using carbon emissions as a raw material. On is the first company in the footwear industry to explore carbon emissions as a primary raw material for a shoe bottom unit, specifically EVA (ethylene vinyl acetate) foam, that could also be used in other shoe parts and products in the future.
CleanCloud Infographic by On
On is convinced that innovation is pivotal to cutting greenhouse gas emissions. CleanCloud is the result of four years of dedicated work, which began with finding the best possible partners. We are adopting a collaborative approach to overcome the challenges of connecting these technologies at commercial scale.
"It's a win-win situation: we are capturing emissions before they pollute our atmosphere and are at the same time moving away from fossil-based materials," explains Caspar Coppetti, Co-Founder and Executive Co-Chairman of On. "Innovation is at the heart of our brand, and after four years of intense research, we are very proud to announce this supply chain coalition with our world-class partners LanzaTech and Borealis."
CleanCloud is the result of a partnership with some of the most innovative companies in biochemicals and plastics innovation, including LanzaTech and Borealis. LanzaTech is using a combination of cutting-edge genetic engineering, state-of-the-art artificial intelligence, and innovations in mechanical and chemical engineering to manufacture chemicals using a process that soaks up carbon rather than emitting it.
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"We are showing the world what is possible when we rethink how we source, use and dispose of carbon," says Jennifer Holmgren, CEO of LanzaTech. "By converting pollution to products, we can see that someday everything in our daily lives will come from recycled carbon. We are excited to be on this journey with On and Borealis to bend the carbon curve, keep our skies blue, and create a sustainable future for all."
Borealis is a leading provider of advanced, circular and renewable plastic solutions and essential in creating high-performance, easy-to-process EVA foam for CleanCloud. This collaboration allows Borealis to further advance its journey in carbon and plastics circularity, and is fully in line with its EverMinds ambition.
Lucrce Foufopoulos, Borealis Executive Vice President Polyolefins, Innovation & Circular Economy Solutions: "Borealis is thrilled to be part of the unique, first-of-its-kind CleanCloud initiative. With our creative partners On and Lanzatech, we are proud to co-create circularity in carbon, and decouple plastic from its reliance on fossil-feedstock. Through innovation and collaboration, we continue re-inventing for more sustainable living."
This is how it works: Technology from LanzaTech captures carbon monoxide emitted from industrial sources like steel mills or emissions from landfill sites before being released into the atmosphere. Once captured, these emissions enter a patented fermentation process. Thanks to specially selected bacteria, the carbon rich gas ferments naturally and is converted to liquid ethanol by the bacteria. This natural fermentation process is similar to that of conventional alcohol production e.g., beer brewing. The ethanol is then dehydrated to create ethylene, which is then polymerized by Borealis to become EVA (a copolymer of ethylene vinyl acetate) the versatile and lightweight material that On starts working with to create a performance foam for shoes.
This is the first major announcement from Swiss brand On following its successful public listing at the New York Stock Exchange in mid-September. On is known for its innovation in the running shoe industry and has become a proven pioneer in sustainable material innovation.
The overall goal is to exchange all bottom units from On shoes currently made from EVA with CleanCloud. This includes the whole Cloud range, THE ROGER franchise collection and a part of the active lifestyle assortment.
Learn more about On's sustainability journey in the "ON Impact Progress Report".
High-res images are available via this link.
About On
On was born in the Swiss Alps with one goal: to revolutionize the sensation of running by empowering all to run on clouds. Eleven years after market launch, On delivers industry-disrupting innovation in premium footwear, apparel, and accessories for high-performance running, outdoor, and all-day activities. Fueled by customer recommendation, On's award-winning CloudTec innovation, purposeful design, and groundbreaking strides in sportswear's circular economy have attracted a fast-growing global fan base inspiring humans to explore, discover and dream on.
On is present in more than 60 countries globally and engages with a digital community on http://www.on-running.com.
About Borealis
Borealis is one of the world's leading providers of advanced and circular polyolefin solutions and a European market leader in base chemicals, fertilizers and the mechanical recycling of plastics. We leverage our polymers expertise and decades of experience to offer value adding, innovative and circular material solutions for key industries. In re-inventing for more sustainable living, we build on our commitment to safety, our people and excellence as we accelerate the transformation to a circular economy and expand our geographical footprint.
With head offices in Vienna, Austria, Borealis employs 6,900 employees and operates in over 120 countries. In 2020, Borealis generated EUR 6.8 billion in sales revenue and a net profit of EUR 589 million. OMV, the Austria-based international oil and gas company, owns 75% of Borealis, while the remaining 25% is owned by a holding company of the Abu-Dhabi based Mubadala. We supply services and products to customers around the globe through Borealis and two important joint ventures: Borouge (with the Abu Dhabi National Oil Company, or ADNOC, based in UAE); and Baystar (with TotalEnergies, based in the US).
http://www.borealisgroup.com | http://www.borealiseverminds.com
About LanzaTechLanzaTech harnesses the power of biology and big data to create climate-safe materials and fuels. With expertise in Synthetic biology, bioinformatics, Artificial Intelligence and Machine Learning coupled with engineering, LanzaTech has created a platform that converts waste carbon into new everyday products that would otherwise come from virgin fossil resources. LanzaTech's first commercial scale gas fermentation plant has produced over 27M gallons of ethanol which is the equivalent of keeping over 130,000 metric tons of CO2 from the atmosphere. A second faclity is operating in China, with additional plants under construction globally. LanzaTech is based in Illinois, USA and employs more than 200 people. Further information is available at http://www.lanzatech.com.
On Logo (PRNewsfoto/On)
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CHOP Researchers Develop a New Class of CAR-T Cells that Target Previously Untargetable Cancer Drivers – Yahoo Finance
Posted: at 9:44 pm
--Focusing on neuroblastoma, the researchers used a multi-omics approach to identify tumor-specific peptides and then used genetic engineering to harness the immune system to destroy tumors--
PHILADELPHIA, Nov. 3, 2021 /PRNewswire/ -- In a breakthrough for the treatment of aggressive solid cancers, researchers at Children's Hospital of Philadelphia (CHOP) have developed a novel cancer therapy that targets proteins inside cancer cells that are essential for tumor growth and survival but have been historically impossible to reach. Using the power of large data sets and advanced computational approaches, the researchers were able to identify peptides that are presented on the surface of tumor cells and can be targeted with "peptide-centric" chimeric antigen receptors (PC-CARs), a new class of engineered T cells, stimulating an immune response that eradicates tumors.
Senior author John M. Maris, MD, pediatric oncologist and Giulio D'Angio Chair in Neuroblastoma Research at CHOP
The discovery, which was described today in Nature, opens the door to treating a broader array of cancers with immunotherapy as well as applying each therapy across a greater proportion of the population.
"This research is extremely exciting because it raises the possibility of targeting very specific tumor molecules, expanding both the cancers that can be treated with immunotherapy and the patient population who can benefit," said Mark Yarmarkovich, PhD, an investigator in the Maris Laboratory at Children's Hospital of Philadelphia and first author of the paper. "By using a multi-omics approach, we were able to identify peptides specific to neuroblastoma tumors, but this method could be used in any cancer, allowing for a more personalized approach to cancer treatment."
The development of CAR T cell-based cancer immunotherapy marked a breakthrough in the treatment of leukemia, but the approach has not yet made significant strides against solid tumors due, at least in part, to a lack of tumor-specific targets. In these cancers, most of the proteins responsible for tumor growth and survival are in the nuclei of tumor cells, not on the cell surface, where they would generally be accessible to CAR T cells. Instead, fragments of these proteins may be presented on the tumor cell surface through the presentation of peptides on the major histocompatibility complex (MHC), which evolved to present viral and bacterial peptides to the immune system. Cancer cells can also present intracellular proteins on MHC, and if these are mutant peptides, they may be recognized as foreign. However, all pediatric cancers and many adult malignancies have few mutations and are rather driven by other factors like dysregulated developmental pathways.
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Neuroblastoma is an explosively aggressive pediatric cancer that is driven by modifications of gene expression that promote uncontrolled tumor growth. Historically, neuroblastoma has been treated with chemotherapy, surgery, and radiation therapy, but patients often relapse with forms of the disease that are chemotherapy resistant. Additionally, the low mutational burden of the cancer, combined with its low MHC expression, have made it difficult to target with immunotherapies.
Despite these obstacles, the researchers hypothesized that some of the peptides presented on the surface of neuroblastoma tumor cells come from proteins that are essential for tumor growth and survival and could be targeted with synthetic CARs. These PC-CARs would allow for direct targeting and killing of tumor cells. The challenge was differentiating tumor-specific peptides from other, similar looking peptides or peptides that exist in normal tissues to avoid cross-reactivity and lethal toxicity.
To do so, the researchers stripped the MHC molecules off neuroblastoma cells and determined which peptides were present and at what abundance. They used a large genomic dataset that the Maris lab has generated to determine which peptides were unique to neuroblastoma and not expressed by normal tissues. They prioritized peptides that were derived from genes essential to the tumor and had characteristics required to engage the immune system. To weed out any potential antigens that might have cross reactivity with normal tissue, the researchers filtered the remaining tumor peptides against a database of MHC peptides on normal tissues, removing any peptide with a parent gene represented in normal tissue.
Using this multi-omics approach, the researchers pinpointed an unmutated neuroblastoma peptide that is derived from PHOX2B, a neuroblastoma dependency gene and transcriptional regulator that was previously identified and characterized at CHOP. The next major hurdle was developing a PC-CAR that specifically recognized just the peptide, which makes up 2-3% of the peptide-MHC complex. In collaboration with antibody-discovery company Myrio Therapeutics, the researchers developed a PC-CAR targeting this peptide and showed that these PC-CARs recognized the tumor-specific peptide on different HLA types, meaning the treatment could be applied to patients of diverse genetic lineages.
Taking the research a step further, the team tested the PC-CARs in mice and found that the treatment led to complete and targeted elimination of neuroblastoma tumors.
"We are excited about this work because it allows us to now go after essential cancer drivers that have been considered 'undruggable' in the past. We think that PC-CARS have the potential to vastly expand the pool of immunotherapies and significantly widen the population of eligible patients," said senior author John M. Maris, MD, pediatric oncologist and Giulio D'Angio Chair in Neuroblastoma Research at CHOP. "Thanks to the Acceleration grant we received through the Cell and Gene Therapy Collaborative at CHOP, we will bring our PHOX2B PC-CAR to a clinical trial at CHOP in late 2022 or early 2023."
Yarmarkovich et al. "Therapeutic Targeting of Intracellular Oncoproteins with Peptide-Centric CAR T Cells," Nature, November 3, 2021, DOI: 10.1038/s41586-021-04061-6
About Children's Hospital of Philadelphia:Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 595-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu
Contact: Jennifer LeeChildren's Hospital of Philadelphia(267) 426-6084LEEJ41@chop.edu
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SOURCE Children's Hospital of Philadelphia
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