Category Archives: Transhuman News

Building tools for biologists: "Our instrument is the early Apple," Inscripta CEO Kevin Ness says. ... [+] "It's the first personal computer for biology."

Kevin Ness has made a career of building tools for biologists. Now, with the burgeoning field of synthetic biology booming, hes ramping up his latest venture, Inscripta, which wants to get a genome-engineering device into the hands of every scientist who wants one. The company has been operating largely under the radar, but with the announcement today that it had raised $125 million in a round led by Paladin Capital Group, for total funding of $260 million, its ready to make its mark.

Our instrument is the early Apple. Its the first personal computer for biology, Ness toldForbesduring a recent meeting in New York City.

Inscriptas Onyx device is small enough to sit on a desktop (roughly three feet by two feet by two feet in size), allowing scientists to modify cells faster and cheaper than would previously have been possible. A select group of researchers has been working with Inscripta to date through an early-access program. The company now expects to get the Onyx (which costs nearly $350,000 for the hardware, plus additional fees for reagents and software) into the market in 2020.

We could sell the platform for $1 million, but that doesnt fulfill our charter of enabling the bioeconomy, says Jason Gammack, Inscriptas chief commercial officer. We believe that biology is going to change the ways we live in ways we dont comprehend.

These are exciting times for the emerging field of synthetic biology. Spurred on by technological and economic advances, particularly the plummeting cost of DNA sequencing and the development of a precision gene-editing tool called Crispr, entrepreneurs have been falling over themselves to start companies. Proponents talk about a new bioeconomy that will allow not just a proliferation of new products but also life-saving antibiotics and a reduction of the environmental harm that comes from our heavy reliance on petrochemicals.

Companies like Ginkgo Bioworks (which I profiled in Forbes magazine over the summer) and Zymergen have set up cell foundries to engineer organisms for new bio-based products. Inscriptas approach is different: Rather than doing biology as a service in highly automated foundries, it wants to get its devices to scientists and researchers, who will be able to use them to run experiments and find answers to burning biological questions in hours rather than years.

Ness, 42, has been able to raise so much money for Inscripta because of his successful history as a biotech entrepreneur. He has a Ph.D. in mechanical engineering from Stanford University and worked as a research scientist at Lawrence Livermore National Laboratory earlier in his career. Then he cofounded two successful biotech companies, 10X Genomics, which went public in September and now trades on Nasdaq with a market cap of $6.1 billion, and QuantaLife, which was acquired by Bio-Rad in 2011 for $162 million plus future milestone payments. He and his teams developed and commercialized products such as droplet digital PCR, a new method for making copies of specific DNA segments, and high-throughput, single-cell gene-expression measurement solutions.

We have watched Kevin execute nearly flawlessly on incredibly complex product roadmaps, says Paul Conley, managing director at Paladin Capital. This is one of the most complex products you are going to see on the marketplace. If we hadnt seen Kevin execute on this level of complexity in the past, we wouldnt be this bullish.

After Ness left 10X Genomics, in the fall of 2016, he was thinking about what to do next when he heard from multiple people (including a headhunter) about a Boulder, Colorado, startup called Muse Bio. Ryan Gill, then a professor at University at Colorado and now scientific director at the Novo Nordisk Foundation Center for Biosustainability, and two of his students had founded Muse in 2015. The company was tiny then, Ness recalls, but it had some patents in genome writing, an area that he was keen to work on. The tools for biologists are atrocious, and theyre worse on writing than reading, he says.

Ness moved from California to Colorado to join the company as CEO, replacing Gill, with the goal of bringing its products to the market. I had this bold vision to create this platform as a stand-alone, to do what Illumina had done for genome-reading, Inscripta wants to do for genome-editing, he says. Genome-sequencing giant Illumina now trades on Nasdaq with a market cap of $48 billion.

Ness recruited Illumina cofounder and former chief operating officer John Stuelpnagel as chairman of the board, and raised $23 million in venture capital from Venrock, the venture capital shop formed by the Rockefellers, to jumpstart operations. Im a big believer in tools. They seem so simple, but they are so enabling, says Stuelpnagel, who is also chairman of the board of 10X Genomics. I think Inscripta has the opportunity to be the next big tool in the toolbox of scientists.

In 2017,Forbes wrotethat Inscripta (as Muse was renamed) had discovered a new Crispr enzyme for editing DNA, known as Crispr-MAD7, and was going to give it away free as it worked to create machines that it could sell to scientists. By this year, still operating in stealth, it had begun working with researchers and academics, including MITs Jim Collins and Chris Voigt and UC Berkeleys Jay Keasling in an early-access program. Early projects focused on areas that included antibiotic resistance and cannabinoids.

This October, Ness raised the profile of the company with a talk at premier synthetic biology conference SynBioBeta. Since then, Ness says, the response has been extremely positive and completely overwhelming, though he declines to say just how many Onyx machines he has commitments to sell.

Markus Herrgard, director of data science and automation at the Novo Nordisk Foundation Center for Biosustainability near Copenhagen, expects to get one of the devices for its lab sometime next year and could eventually roll out more of them. The way we envision using the technology Inscripta has is to accelerate the process, he says. Instead of making one [genetic] change at a time we can make tens of thousands at a time. In terms of speed, this is definitely a sea change.

The first version of Onyx will work on microbial cells, but Inscripta plans to launch a future product that could work with mammalian cells, a far more complex area that will allow researchers to develop sophisticated therapeutics. What we want, says Ness, is the next industrial revolutionthe bio-based industrial revolution.

Originally posted here:
Serial Biotech Entrepreneur Kevin Ness Has Raised $260 Million To Get His Genome-Engineering Device Into The Hands Of Every Scientist Who Wants One -...

An artist's illustration of a DNA double helix. New technology makes it easy to edit the human genome, even the germline which can affect all of human evolution. (Image:. U.S. National Human Genome Research Institute/Reuters

By making genetic research so much easier, the recent technology known as CRISPR has allowed scientists an enormous advantage in research into so many areas.

Unfortunately theres a downside which raises serious ethical questions.

Franoise Baylis (CM, ONS, PhD, FRSC, FCAHS), is a research professor at Dalhousie University Halifax who has written on the subject.

The concern with gene-editing is with experiments into modification of human DNA, which could lead in theory to changing of the human genome forever. It could in theory enable creating designer babies. Indeed its been just over a year since the first genome edited babies were created by a Chinese scientist. A Russian researcher has since announced plans to carry out similar human gene editing experiments. Other Chinese experiments involve putting human genes into monkeys. All of these, and other potential experiments, have raised the concern of the scientific world that some of its members are going beyond ethical concerns of science.

Research professor Francoise Baylis at Dalhousie University, Halifax

While some experts have expressed concern about state manipulation to create specific charachteristics, Professor Bayliss suggests that designer babies could result in greater class divide. This would be due to the expense making such technology accessible to the upper echelons and entrenching elite advantage, and thus privilege, in their DNA.

However she says these experiments have resulted in governments and the scientific community coming out with regulations and recommendations to slow down or halt such research until such time as serious ethical discussions take place to establish limits on what should be done and how.

F Baylis on the ethical questions involving CRISPR technology and gene editing of the human genome , Harvard University Press

She says the human genome belongs to all of us and any single or small group of scientists shouldnt be altering it on their own.

As a direct consequence of increasingly audacious moves by some scientists to engineer future generations, important decisions must now be made decisions that will set a new course for science, society, and humanity. May these decisions be inclusive and consensual. May they be characterized by wisdom and benevolence. And, may we never lose sight of our responsibilities to us all. F Bayliss: Altered Inheritance: CRISPR and the Ethics of Human Genome Editing F Bayliss: Altered Inheritance: CRISPR and the Ethics of Human Genome Editing

Fortunately some action has been taken. The WHO has convened a multi-disciplinary Expert Advisory Committee on Human Genome Editing to examine the scientific, ethical, social and legal challenges associated with human genome editing (both somatic and germ cell). Professor Bayliss is a member of the group which met for the first time this spring.

She lauds those countries that have established regulations regarding such research but notes there is always the chance of rogue scientists.

She also notes that scientists are usually very concerned about recognition by their peers and being shunned for having crossed established ethical lines is something they would very likely avoid

Additional information

The Conversation: F Bayliss: Dec 10/19: A year after the first CRISPR babies, stricter regulations are now in place

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CRISPR: Ethics and the gene editing of humans - Radio Canada International (en)

Gene editing using the CRISPR system has been established as the most powerful tool in the search for new drugs and is now being exploited for therapeutic purposes. Here, Pushpanathan Muthuirulan discusses the promises and wider opportunities of using CRISPR technology to open up the possibility of large-scale screening of drug targets. He also highlights the importance of implementing CRISPR technology into clinical practice for development of next-generation therapeutics and patient-tailored medicine.

THE DRUG discovery process, in which new drug candidates are discovered and evaluated for therapeutic use, has resulted in both promising and life-saving therapies for numerous diseases including inherited genetic disorders and pathogenic infections.1 However, the discovery and testing of a new drug candidate typically takes more than a decade and the total cost associated with drug discovery processes can exceed $1 billion.2 In the United States, the drug discovery process takes an average of 12 years and in excess of $1 billion to develop a new drug.3 Furthermore, only a few drug candidates actually make it to market; the chance of a new drug actually reaching market is only one in 5,000. The high cost and lengthy effort of getting new drugs to market make the drug development process a risky endeavour for pharmaceutical companies, which consequently hinders discovery and development of new therapies. The recent emergence of genome editing technologies and advances in our understanding of human genome sequences have raised hope that direct manipulation of the genome could potentially revolutionise the process of drug discovery and therapeutics.4 In particular, new technologies like CRISPR-Cas9 are key to unlocking potential drug targets and could have a profound impact on modern drug discovery and development.1,5

Originally posted here:
CRISPR: kick-starting the revolution in drug discovery - Drug Target Review

9 December 2019

It's just over a year since Dr He Jiankui's controversial announcement that he had created the world's first genome-edited babies (see BioNews 977). This has sparked international debate over the use of the approach in humans but what may be missing in the discussion are moral questions concerning the research that would precede clinical applications.

Genome editing is a method that allows scientists to alter the DNA of organisms. Researchers are using various technologies in their studies, including the use of CRISPR/Cas9, removing mutated genes that cause heritable diseases and conditions, eg Parkinson's or muscular dystrophy.

However, there are risks associated with CRISPR. To advance genetic methods that are safe and effective for humans, much research is needed. It is possible to cut DNA at the wrong spot: off-target effects where edits are performed in the wrong place and scientists are uncertain as to how this might potentially affect patients. The other challenge is mosaicism where only some cells carry the edit but not others.

Accordingly, fundamental research is required to check the safety and accuracy of genome editing. And clinical applications can be considered only after thorough studies have been conducted.

However, there are important ethical issues to be discussed concerning the studies that would precede this stage. For instance, scientists may need to do testing on human embryos. For such experiments, many eggs are required for fertilisation in the lab to produce these embryos.

Recently, Dr Emilia Niemiec and Dr Heidi Carmen Howard at Uppsala University in Sweden, raised these ethical matters in their Correspondence to Nature. The authors stressed that women who decide on egg donation should comprehend the ethical issues to enable them to make an informed decision on whether or not to donate their eggs.

Egg donation involves health risks for these women and the financial compensation they may receive could amount to an inducement for economically disadvantaged donors. Thus, the studies, which are likely to precede clinical applications of genome editing in humans, pose their own set of ethical issues.

An essential factor to consider is whether, before egg donation, adequate counselling was presented to the donors to ensure they were fully informed about the health risks involved. These risks are due to ovarian stimulation to obtain the eggs.

The process of egg retrieval is invasive and painful. Elevated doses of ovary stimulating drugs are needed to induce the ovaries to create numerous eggs. Some egg donors may experience ovarian hyperstimulation syndrome (OHSS), a condition that could cause nausea, bloating, kidney failure and even death (see BioNews 973 and 975).

There have been reported deaths of patients after undergoing IVF treatment. A possible long-term risk of ovary stimulating drugs is the development of cancer. Some studies have suggested a link between fertility drugs and certain types of cancers, though researchers speculate that these may not develop until donors are in their 50s or 60s.

Egg collection and ovarian stimulation are associated with more health risks than the removal of other human tissues for research. Egg donors are exposed to an increased risk of morbidity or mortality associated with the stimulating hormone treatment needed for egg retrieval. If they were not sufficiently told of the various health risks, it is questionable whether informed consent is actually provided by the women.

Despite the frequent use of ovarian stimulation and egg retrieval in IVF cycle, there has been a shortage of studies done on the short- and long-term adverse consequences of ovarian stimulation and egg donation. So there are uncertainties surrounding the effects of the drugs and procedures.

The issue of pecuniary gain for egg donors in research raises the concerns of commodification of human tissues and commercialisation of research. Donations of body parts and tissues to research are expected to be altruistic. Commodification refers to an attachment of economic value to a thing which locates outside the economic sphere.

The value of some matters, such as the human body, cannot and should not be expressed in terms of money. Human eggs should not be sold by donors. Some women may be primarily enticed by money to donate their eggs without receiving adequate information ie, the health risks associated with egg extraction. This is especially true for poorer women who may ultimately sell their eggs out of desperation.

At the very least, egg donors should be reimbursed for their services. Egg donors receive no direct therapeutic benefit from the study. But in contrast to sperm or blood donation, the process of egg donation is far more complex and risky. It is essential to differentiate between payment for the commodity of the gamete and payment for the service provided, that is, reimbursement. Egg donors should not be out-of-pocket after donation, so their participation is expense neutral. However, payment beyond reasonable costs should not be permitted to prevent the risk of exploitation of women and the commodification of human eggs.

Eggs donated from younger donors are preferred as they are considered as being of better quality compared with eggs from older women. With these ethical issues surrounding egg donation in genome editing research, it is critical there is sufficient regulatory framework in place to safeguard the rights of egg donors.

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Human genome editing: What about the protection of egg donors in research? - BioNews

Its been just over a year since the dramatic announcement of the worlds first genome-edited babies using CRISPR technology. Since then, to the chagrin of some and the relief of others, there have been no more such announcements. This is due, in no small part, to discreet actions taken by the Peoples Republic of China, the World Health Organization (WHO) and the Russian Federation.

Read more: What is CRISPR gene editing, and how does it work?

In late November 2018, He Jiankui, a Chinese biophysicist, confirmed hed created genetically modified twins in an effort to provide the children with resistance to HIV. A few days later, he presented some of his work at the Second International Summit on Genome Editing in Hong Kong. At this meeting, He mentioned another ongoing pregnancy involving the use of a genetically modified embryo. To this day, we do not know the outcome of this pregnancy.

What we do know is that Chinas Ministry of Science and Technology condemned Hes actions and shortly thereafter, Chinas National Health Commission drafted new regulations on the clinical use of emerging biomedical technologies, including human genome editing. The final text of the Administrative Regulations for the Clinical Application of New Biomedical Technologies is not yet available and it is not known when these regulations will come into effect.

Based on the draft text open to public comment, research of the type conducted by He would require approval from Chinas highest administrative authority.

In the wake of Hes controversial experiment, the WHO convened a multi-disciplinary Expert Advisory Committee on Human Genome Editing to examine the scientific, ethical, social and legal challenges associated with human genome editing (both somatic and germ cell).

Specifically, the committee was tasked by the director general, Tedros Adhanom Ghebreyesus, to advise and make recommendations on appropriate governance mechanisms. The committee (of which I am a member) met for the first time in March 2019.

In June 2019, Russian molecular biologist Denis Rebrikov announced his plans to follow in Hes footsteps. Rebrikov would genetically modify early-stage human embryos in his lab and use those embryos to initiate a pregnancy that hopefully would result in the birth of healthy HIV-resistant offspring. Unlike He, however, Rebrikov planned to involve HIV-infected women in his research in an effort to address the risk of transmission of the virus in utero from the pregnant woman to her fetus. (Hes research involved HIV infected men.)

In response, on advice from the WHO Expert Advisory Committee, the WHO director general issued a statement calling on regulatory and ethics authorities in all countries to refrain from approving research on heritable human genome editing until its ethical and social implications had been properly considered.

Read more: Opening Pandora's Box: Gene editing and its consequences

Undeterred by the WHO announcement, in September and October 2019 Rebrikov, confirmed his intention to apply for permission to proceed with heritable human genome editing, but with a different focus. Though it was initially reported that Rebrikov felt a sense of urgency to help women with HIV, he was unable to find HIV-positive women who did not respond to standard anti-HIV drugs and who wanted to get pregnant to participate in his research.

So, instead of modifying the CCR5 gene which would provide future offspring with resistance to HIV, Rebrikov planned to modify the GJB2 gene to correct a mutation that causes a type of hereditary deafness. According to Rebrikov, there were several couples interested in participating in this research.

Meanwhile, the Russian government issued a statement making it clear that Rebrikov would not get regulatory approval for the proposed research.

In October 2019, the Ministry of Health of the Russian Federation affirmed that the use of heritable genome editing was premature. Further, the ministry officially endorsed the WHO position that it would be irresponsible and unacceptable to use genome-edited embryos to initiate human pregnancies.

Finally and most importantly the Ministry of Health explicitly stated that the WHO position, supported by the Russian Federation, should be decisive in the formation of country policies in this area.

This strong statement by the Ministry of Health of the Russian Federation is reassuring. It sets an important example for regulatory authorities around the world who support the WHOs efforts to develop effective governance instruments to deter and prevent irresponsible and unacceptable uses of genome editing of embryos to initiate human pregnancies.

In the last lines of my new book Altered Inheritance: CRISPR and the Ethics of Human Genome Editing I write:

As a direct consequence of increasingly audacious moves by some scientists to engineer future generations, important decisions must now be made decisions that will set a new course for science, society, and humanity. May these decisions be inclusive and consensual. May they be characterized by wisdom and benevolence. And, may we never lose sight of our responsibilities to us all.

Collectively, all of us (experts and non-experts) have a responsibility to make the best use of emerging technologies to improve the health and well-being of all people everywhere. This can only be achieved through collaborative effort on a global scale.

We need time to carefully consider the kind of world we want to live in and how human genome editing technology might or might not help us build that world. We cant do this work properly if scientists brashly go about the business of making genome-edited babies.

[ Youre smart and curious about the world. So are The Conversations authors and editors. You can read us daily by subscribing to our newsletter. ]

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A year after the first CRISPR babies, stricter regulations are now in place - The Conversation CA

Identifying the Genomic Landscape of CDK4/6i Resistance in Patients with HR+/HER2- Metastatic Breast Cancer

After performing whole exome sequencing (WES) on metatatic tumor biopsies from 58 patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer who received a CDK4/6i with or without an antiestrogen, the researchers characterized 69.5% as resistant (either intrinsic or acquired) and 30.5% as sensitive. In order to validate putative resistance mediators found in patient samples, HR-positive/HER2-negative cells were modified via CRISPR knockout or lentiviral overexpression.

In parallel, HR-positive/HER2-negative breast cancer cells were cultured to resistance in the presence of an escalating dose of CDK4/6i. Derivative cell lines were subjected to western blotting in an effort to interrogate the putative resistance mediators. Novel dependencies were found in these derivative cell lines by using treatment with targeted therapeutic agentsin vitro.

Following these methods, the WES of tumors with CDK4/6i exposure revealed candidate mechanisms of resistance including biallelicRB1disruption (n=4, 10%). They also revealed activating events inAKT1(n=5, 12.5%), RAS (n=4, 10%), aurora kinase A (AURKA,n=11, 27.5%), and cyclin E2 (CCNE2, n=6, 15%).

Knockout ofRB1and overexpression of the activating events caused CDK4/6i demonstrated concordant acquisition of RB1 downregulation, RAS/ERK activation, AURKA overexpression, and CCNE2 overexpression.

Based on these results, the researchers were able to state that the genomic landscape of resistance to CDK4/6i is heterogeneous with multiple potential mediators that play well-established roles in cell division and oncogenic signal transduction. They found novel mechanisms of clinical resistance, including activation of AKT1 and RAS family oncogenes, as well as amplification of AUKRA and CCNE2.In vitro, these drivers provoked CDK4/6i resistance. Finally, in each case, a novel dependency was identified, which was translatable into the clinic setting.

The researchers argued that the results demonstrate the future potential of next-generation sequencing as a tool to enable identification of resistance mediators. Similarly, they said that the presence of specific genomic alterations may define new therapeutic opportunities in CDK4/6i resistance.

REFERENCEWander SA, Cohen O, Gong X, Johnson GN, et al. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC). Accessed Dec 4, 2019.https://plan.core-apps.com/sabcs2019/abstract/c3d31d6ffb8feb46fe802df1c905011e

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Identifying the Genomic Landscape of CDK4/6i Resistance in Patients with HR+/HER2- Metastatic Breast Cancer - Pharmacy Times

Data from the MINDACT trial revealed that among women with luminal breast cancers (hormone receptorpositive, HER2-negative by local pathology) with a high clinical risk and low genomic risk, those aged 40 to 50 years had a greater benefit from chemotherapy than patients older than 50.

This caused researchers, including study author Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center/Champalimaud Foundation, to conduct an unplanned analysis of the MINDACT trial to determine if the addition of chemotherapy did in fact have an age-dependent benefit on distant metastasis-free survival (DMFS) among certain patients with breast cancer, as was seen in the TAILORx trial analysis.

The MINDACT trial compares the utility of the 70-gene signature commercial diagnostic test, MammaPrint, with common clinical-pathological criteria to select patients with breast cancer who have 0 to 3 positive nodes for adjuvant chemotherapy. In the analysis cohort, patients older than 40 were chosen, as there was only 2 DMFS events in patients under 40, attributing to a total population of 1264 patients, 399 aged 40 to 50 and 865 aged older than 50, from the MINDACT trial.

The trials inclusion of women aged under 50 served crucial to analyses, as Cardoso noted that younger women with breast cancer are underrepresented in clinical trials, and treatment decisions are often based on data obtained in older, postmenopausal women. It is important to examine how age impacts treatment efficacy and disease recurrence in patients with breast cancer to determine the best treatment option for each patient, said Cardoso.

In the analysis, researchers evaluated 5-year DMFS of patients with hormone receptorpositive, HER2-negative breast cancer enrolled in the MINDACT trial who had a low genomic and a high clinical risk. These patients were randomized to receive chemotherapy based on either clinical or genomic risk.

Researchers found that among women at least 50 years of age, estimated 5-year DMFS was similar between patients who received (95.2%) and who did not receive (95.4%) chemotherapy. In patients 40 to 50 years of age, estimated 5-year DMFS for those who received chemotherapy was 96.2% as opposed to 92.6% in those who did not receive chemotherapy, a heightened benefit like that found in the TAILORx trial.

Similar to the TAILORx trial, we found that women classified as high risk of recurrence by traditional clinical-pathological factors but low risk by MammaPrint had a worse outcome if treated with tamoxifen alone, and that the benefit of chemotherapy may eventually be higher in this group, said Cardoso. Tamoxifen treatment alone is common in younger women with only 7% of those in the MINDACT trial also receiving an LHRH analog. This is a trend that may suggest that women, presumably premenopausal, might be undertreated with tamoxifen alone.

However, Cardoso noted that results are not confirmed yet, as in both the MINDACT and TAILORx trials, the majority of women received tamoxifen alone (without ovarian suppression) as adjuvant chemotherapy. While researchers are unable to clarify if the results seen in younger women are due to the direct effect of chemotherapy or through chemotherapy-induced ovarian suppression, the growing evidence from the 2 trials indicates that younger women with high clinical risk and low genomic risk, or with an intermediate RS, may benefit from additional treatment.

The added value of chemotherapy in case of optimal endocrine therapy (i.e. OFS + tamoxifen or aromatase inhibitor) cannot be evaluated in MINDACT nor in TailorX and should be further studied, said the study authors.

Reference

Piccart MJ, Poncet C, Cardoso F, et al. Should age be integrated together with clinical and genomic risk for adjuvant chemotherapy decision in early luminal breast cancer? MINDACT results compared to those of TAILOR-X. Presented at: San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS4-05.

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Age Associated to Benefit Derived From Chemotherapy for Women With Luminal Breast Cancer, MINDACT Trial Finds - AJMC.com Managed Markets Network

Predicting a persons likelihood of developing disease, long before signs and symptoms appear, has moved closer following a research discovery by Irish scientists.

A team at Queens University Belfast examined how certain DNA elements work to regulate gene expression within the genome and how this predisposes people to diseases.

They say this information could help predict a persons risk of cancer, diabetes and heart disease, and could lead to earlier diagnosis before signs and symptoms of disease appears. The research has been published in the iScience journal.

Many diseases occur when things go wrong within a cell or set of cells in the body. Previous research has determined that many diseases result from mutations to a part of the DNA strand known as an enhancer.

Enhancers function as a turn on switch in gene expression and activate the promoter region of a particular gene. This means certain genetic traits can be turned on or turned off, which in turn shapes a persons early development and lifetime health including their chance of developing a certain disease.

The researchers discovered that enhancer DNA elements exhibit high propeller twist (ProT) levels, which is the angle of twisting of two neighbouring DNA bases about their long axis, like the propeller blades of an aeroplane.

Because of high ProT levels, the surface of these enhancer sections on the DNA strands become more physically accessible and flexible, thus allowing easier access for proteins that bind to DNA. As a result, they may be more prone to mutagenic agents harming cells and causing cancer and other diseases.

These findings answer many fundamental biological questions around the function of DNA in health and disease, said Dr Vijay Tiwari, reader at Wellcome-Wolfson Institute for Experimental Medicine at Queens and lead author on the paper.

Our study is the first of its kind to provide insight into the role physical DNA features play in proper development of specific cell-types of the body and how their malfunctions may underlie diseases.

The researchers also discovered that as cells become abnormal, they switch to using low ProT regions as enhancer elements. This may help with the development of early diagnosis of diseases.The research was carried out in collaboration with researchers from the Ludwig Maximilian University of Munich in Germany.

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Disease prediction brought closer by Irish research discovery - The Irish Times