Category Archives: Transhuman News

Life goes on as gene-edited foods begin to hit the market. Japanese consumers have recently started buying tomatoes that fight high blood pressure, and Americanshave been consuming soyengineered to produce high amounts of heart-healthy oils for a little over two years. Few people noticed these developments because, as scientists have said for a long time, the safety profile of a crop is not dictated by the breeding method that produced it. For all intents and purposes, it seems that food-safety regulators have done a reasonablejob of safeguarding public health against whatever hypothetical risks gene editing may pose.Credit: Karuchibe

But this has not stopped critics of genetic engineering from advocating for more federal oversight of CRISPR and othertechniquesused to make discrete changes to the genomes of plants, animals and other organisms we use for food or medicine. Over at The Conversation, a team of scientists recently made the case for tighter rules inCalling the latest gene technologies natural is a semantic distraction they must still be regulated.

Many scientists have defended gene editing, in part, by arguing that it simply mimics nature. A mutation that boosts the nutrient content of rice, for example, is the same whether it was induced by a plant breeder or some natural phenomenon. Indeed, the DNA of plants and animals we eatcontains untold numbersof harmless, naturally occurringmutations. But The Conversation authors will havenone of this:

Unfortunately, the risks from technology dont disappear by calling it natural Proponents of deregulation of gene technology use the naturalness argument to make their case. But we argue this is not a good basis for deciding whether a technology should be regulated.

They have written a very longpeer-reviewed articleoutlining a regulatory framework based on scale of use.The ideais that the more widely a technology is implemented, the greater risk it may pose to human health and the environment, which necessitates regulatory control points to ensure its safe use. Its an interesting proposal, but its plagued by several serious flaws.

The most significant issue with a scale-based regulatory approachis that its a reaction to risks that have never materialized. This isnt to say that a potentially harmful genetically engineered organism will never be commercialized. But if were going to upend our biotechnology regulatory framework, we need to do so based on real-world evidence. Some experts have actually argued, based on decades of safety data, that the US over-regulates biotech products. As biologist and ACSHadvisorDr. Henry Miller and legal scholar John Cohrssen wroterecently in Nature:

After 35 years of real-world experience with genetically engineered plants and microorganisms, and countless risk-assessment experiments, it is past time to reevaluate the rationale for, and the costs and benefits of, the case-by-case reviews of genetically engineered products now required by the US Environmental Protection Agency (EPA), US Department of Agriculture (USDA) and US Food and Drug Administration (FDA).

Real-world data aside for the moment, there are some theoretical problems with the scalabilitymodel as well. Theargument assumes thatrisks associated with gene editing proliferate as use of the technology expands, because each gene edit carries a certain level of risk. This is a false assumption, as plant geneticist Kevin Folta pointed out on a recentepisode of the podcastwe co-host (21 minute mark).

Scientists have a variety of tools with which to monitor and limit the effects of specific gene edits. For example,proteins known asanti-CRISPRs can be utilized to halt the gene-editing machinery so it makes only the changes we want it to. University of Toronto biochemist Karen Maxwell has explained how this couldwork in practice:

In genome editing applications, anti-CRISPRs may provide a valuable off switch for Cas9 activity for therapeutic uses and gene drives. One concern of CRISPR-Cas gene editing technology is the limited ability to control its activity after it has been delivered to the cell . which can lead to off-target mutations. Anti-CRISPRs can potentially be exploited to target Cas9 activity to particular tissues or organs, to particular points of the cell cycle, or to limit the amount of time it is active

Suffice it to say that these and other safeguards significantly alter the risk equation and weaken concerns about a gene-edits-gone-wild scenario. Parenthetically, scientists design these sorts of preventative measures as they developmoregenetic engineering applications for widespread use. This is why the wide variety of cars in production todayhave safety featuresthat would have been unheard of in years past.

To bolster their argument, The Conversation authors made the following analogy:

Imagine if other technologies with the capacity to harm were governed by resemblance to nature. Should we deregulate nuclear bombs because the natural decay chain of uranium-238 also produces heat, gamma radiation and alpha and beta particles? We inherently recognize the fallacy of this logic. The technology risk equation is more complicated than a supercilious its just like nature argument

If someone has to resort to this kind of rhetoric, the chances are excellent that their argument is weak. Fat Man and Little Boy,the bombs droppedon Japan in 1945, didnt destroy two cities because a nuclear physicist in New Mexico made a technical mistake. These weapons are designed to wreak havoc. Tomatoes bred to produce more of an amino acid, in contrast, are not.

The point of arguing that gene-editing techniques mimic natural processes isnt to assert that natural stuff is good; therefore, gene editing is also good. Instead, the point is to illustrate that inducing mutations in the genomes of plants and animals is not novel or uniquely risky. Even the overpriced products marketed as all-naturalhave been improvedby mutations resulting from many years of plant breeding.

Nonetheless, some scientistshave arguedthat reframing the gene-editing conversation in terms of risk vs benefit would be a smarter approach than making comparisons to nature. I agree with them, so lets start now. The benefits of employing gene editing to improve our food supply and treat disease far outweigh the potential risks, which we can mitigate. Very little about modern life is naturaland its time we all got over it.

Cameron J. English is the director of bio-sciences at theAmerican Council on Science and Health. Visithis websiteand follow ACSH on Twitter@ACSHorg

A version of this article was originally posted at theAmerican Council on Science and Healthand is reposted here with permission. The American Council on Science and Health can be found on Twitter@ACSHorg

More:
Viewpoint: An argument for CRISPR crops 'Very little about modern life is natural and it's time we all got over it' - Genetic Literacy Project

Gene therapy is a powerful developing technology that has the potential to address myriad diseases. For example, Huntington's disease, a neurodegenerative disorder, is caused by a mutation in a single gene, and if researchers could go into specific cells and correct that defect, theoretically those cells could regain normal function.

A major challenge, however, has been creating the right "delivery vehicles" that can carry genes and molecules into the cells that need treatment, while avoiding the cells that do not.

Now, a team led by Caltech researchers has developed a gene-delivery system that can specifically target brain cells while avoiding the liver. This is important because a gene therapy intended to treat a disorder in the brain, for example, could also have the side effect of creating a toxic immune response in the liver, hence the desire to find delivery vehicles that only go to their intended target. The findings were shown in both mouse and marmoset models, an important step towards translating the technology into humans.

A paper describing the new findings appears in the journal Nature Neuroscience on December 9. The research was led by Viviana Gradinaru (BS '05), professor of neuroscience and biological engineering, and director of the Center for Molecular and Cellular Neuroscience.

The key to this technology is the use of adeno-associated viruses, or AAVs, which have long been considered promising candidates for use as delivery vehicles. Over millions of years of evolution, viruses have evolved efficient ways to gain access into human cells, and for decades researchers have been developing methods to harness viruses' Trojan-Horse-like abilities for human benefit.

AAVs are made up of two major components: an outer shell, called a capsid, that is built from proteins; and the genetic material encased inside the capsid. To use recombinant AAVs for gene therapy, researchers remove the virus's genetic material from the capsid and replace it with the desired cargo, such as a particular gene or coding information for small therapeutic molecules.

"Recombinant AAVs are stripped of the ability to replicate, which leaves a powerful tool that is biologically designed to gain entrance into cells," says graduate student David Goertsen, a co-first author on the paper. "We can harness that natural biology to derive specialized tools for neuroscience research and gene therapy."

The shape and composition of the capsid is a critical part of how the AAV enters into a cell. Researchers in the Gradinaru lab have been working for almost a decade on engineering AAV capsids that cross the blood-brain barrier (BBB) and to develop methods to select for and against certain traits, resulting in viral vectors more specific to certain cell types within the brain.

In the new study, the team developed BBB-crossing capsids, with one in particular AAV.CAP-B10that is efficient at getting into brain cells, specifically neurons, while avoiding many systemic targets, including liver cells. Importantly, both neuronal specificity and decreased liver targeting was shown to occur not just in mice, a common research animal, but also in laboratory marmosets.

"With these new capsids, the research community can now test multiple gene therapy strategies in rodents and marmosets and build up evidence necessary to take such strategies to the clinic," says Gradinaru. "The neuronal tropism and decreased liver targeting we were able to engineer AAV capsids for are important features that could lead to safer and more effective treatment options for brain disorders."

The development of an AAV capsid variant that works well in non-human primates is a major step towards the translation of the technology for use in humans, as previous variants of AAV capsids have been unsuccessful in non-human primates. The Gradinaru lab's systematic in vivo approach, which uses a process called directed evolution to modify AAV capsids at multiple sites has been successful in producing variants that can cross the BBBs of different strains of mice and, as shown in this study, in marmosets.

"Results from this research show that introducing diversity at multiple locations on the AAV capsid surface can increase transgene expression efficiency and neuronal specificity," says Gradinaru. "The power of AAV engineering to confer novel tropisms and tissue specificity, as we show for the brain versus the liver, has broadened potential research and pre-clinical applications that could enable new therapeutic approaches for diseases of the brain."

The paper is titled "AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset." Goertsen; Nicholas Flytzanis (PhD '18), the former scientific director of the CLARITY, Optogenetics and Vector Engineering Research(CLOVER)Center of Caltech's Beckman Institute; and former Caltech postdoctoral scholar Nick Goeden are co-first authors. Additional coauthors are graduate student Miguel Chuapoco, and collaborators Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Ip, and James Pickel.

Funding was provided by the Defense Advanced Research Projects Agency, the National Institutes of Health, and the National Sciences and Engineering Research Council of Canada.

Flytzanis, Goeden, and Gradinaru are co-founders of Capsida Biotherapeutics, a Caltech-led startup company formed to develop AAV research into therapeutics.

Follow this link:
New Technology is One Step Closer to Targeted Gene Therapy - Caltech

One 2021 study looked at the genome of Solanum sitiens a wild tomato species which grows in the extremely harsh environment of the Atacama Desert in Chile, and can be found at altitudes as high as 3,300m (10,826ft). The study identified several genes related to drought-resistance in Solanum sitiens, including one aptly named YUCCA7 (yucca are draught-resistant shrubs and trees popular as houseplants).

They are far from the only genes that could be used to give the humble tomato a boost. In 2020 Chinese and American scientists performed a genome-wide association study of 369tomato cultivars, breeding lines and landraces, and pinpointed a gene called SlHAK20 as crucial for salt tolerance.

Once the climate-smart genes such as these are identified, they can be targeted using Crispr to delete certain unwanted genes, to tune others or insert new ones. This has recently been done with salt tolerance, resistance to various tomato pathogens, and even to create dwarf plants which could withstand strong winds (another side effect of climate change). However, scientists such as Cermak go even further and start at the roots they are using Crispr to domesticate wild plant species from scratch, "de novo" in science speak. Not only can they achieve in a single generation what previously took thousands of years, but also with a much greater precision.

De novo domestication of Solanum pimpinellifolium was how Cermak and his colleagues at the University of Minnesota arrived at their 2018 plant. They targeted five genes in the wild species to obtain a tomato that would be still resistant to various stresses, yet more adapted to modern commercial farming more compact for easier mechanical harvesting, for example. The new plant also had larger fruits than the wild original.

"The size and weight was about double," Cermak says. Yet this still wasn't the ideal tomato he strives to obtain for that more work needs to be done. "By adding additional genes, we could make the fruit even bigger and more abundant, increase the amount of sugar to improve taste, and the concentration of antioxidants, vitamin C and other nutrients," he says. And, of course, resistance to various forms of stress, from heat and pests to draught and salinity.

Read more here:
The tomatoes at the forefront of a food revolution - BBC News

In an effort to improve treatment for obsessive compulsive disorder (OCD), researchers headed by teams at Brown University, and Baylor College of Medicine, have for the first time recorded electrical signals in the human brain that are associated with ebbs and flows in OCD symptoms, over an extended period, while individuals went about daily living in their homes. The research could be an important step in making an emerging therapy called deep brain stimulation (DBS) responsive to everyday changes in OCD symptoms.

In addition to advancing DBS therapy for cases of severe and treatment resistant OCD, this study has the potential for improving our understanding of the underlying neurocircuitry of the disorder, said Wayne Goodman, PhD, at Baylor College of Medicine. This deepened understanding may allow us to identify new anatomic targets for treatment that may be amenable to novel interventions that are less invasive than DBS. Goodman is co-author of the researchers published paper in Nature Medicine, which is titled, Long-term ecological assessment of intracranial electrophysiology synchronized to behavioural markers in obsessive-compulsive disorder.

OCD causes recurring unwanted thoughts and repetitive behaviors, and is a leading cause of disability. The condition, which is often debilitating, may affect perhaps 2-3% of the worlds population, the authors noted. Up to 20-40% of cases dont respond to traditional drug or behavioral treatments. Approximately 10% of individuals fail to achieve benefit from any intervention.

Deep brain stimulation, a technique that involves delivering mild electrical pulses via small electrodes precisely placed in the brain, can be effective in treating more than 50% of patients for whom other therapies failed. Over half of patients with treatment-resistant OCD are responders to DBS targeted to the ventral capsule/ventral striatum (VC/VS) region, the researchers further noted. To date, however, the number of patients who have received DBS for OCD is still in the hundreds.

One limitation of DBS is that it is unable to adjust to moment-to-moment changes in OCD symptoms, which are impacted by the physical and social environment. But adaptive DBS which can adjust the intensity of stimulation in response to real-time signals recorded in the braincould be more effective than traditional DBS and reduce unwanted side effects.

OCD is a disorder in which symptom severity is highly variable over time and can be elicited by triggers in the environment, said David Borton, PhD, an associate professor of biomedical engineering at Brown University, a biomedical engineer at the US Department of Veterans Affairs Center for Neurorestoration and Neurotechnology and a senior author of the new research. A DBS system that can adjust stimulation intensity in response to symptoms may provide more relief and fewer side effects for patients. But in order to enable that technology, we must first identify the biomarkers in the brain associated with OCD symptoms, and that is what we are working to do in this study. As the authors noted, An electrophysiological biomarker of symptom state would enable aDBS for OCD and other psychiatric disorders, which may provide a better approach for treating fluctuations in symptom intensity.

The research, led by Nicole Provenza, a recent Brown biomedical engineering PhD graduate from Bortons laboratory, was a collaboration between Bortons research group, affiliated with Browns Carney Institute for Brain Science and School of Engineering; the research groups of Wayne Goodman PhD, and Sameer Sheth MD, PhD, at Baylor College of Medicine; and Jeff Cohn, PhD, from the University of Pittsburghs Department of Psychology and Intelligent Systems Program and Carnegie Mellon University.

For their study, Goodmans team recruited five participants with severe OCD who were eligible for DBS treatment. Sheth, lead neurosurgeon, implanted in each participant an investigational DBS device from Medtronic, which is capable of both delivering stimulation and recording native electrical brain signals. Using the sensing capabilities of the hardware, the team gathered brain-signal data from participants in both clinical settings and at home as they went about daily activities. The DBS implants used in our study allow for real-time frequency-domain analysis of electrophysiological activity recorded simultaneously during stimulation delivery from the implanted electrodes, they wrote.

Along with the brain signal data, the team also collected a suite of behavioral biomarkers. In the clinical setting, these included facial expression (automatic facial affect recognition; AFAR) and body movement. Using computer vision and machine learning, they discovered that the behavioral features were associated with changes in internal brain states. At the participants homes, the team measured self-reports of OCD symptom intensity as well as biometric dataheart rate and general activity levelsrecorded by a smart watch and paired smartphone application, provided by Rune Labs. All of those behavioral measures were then time-synched to the brain-sensing data, enabling the researchers to look for correlations between the two.

Here, we acquired electrophysiological data with behavioral readouts over both short and long timescales, the team commented. In the clinic, we examined changes in affect (AFAR) during DBS parameter changes over short timescales (seconds to minutes). At home during participant-controlled recordings, we captured behavioral changes (self-reported OCD symptoms) over longer timescales (days to weeks to months) in natural settings, collected continuous data during natural and planned exposures, and developed methods to synchronize behavioral metrics to intracranial electrophysiology.

This is the first time brain signals from participants with neuropsychiatric illness have been recorded chronically at home alongside relevant behavioral measures, Provenza said. Using these brain signals, we may be able to differentiate between when someone is experiencing OCD symptoms, and when they are not, and this technique made it possible to record this diversity of behavior and brain activity.

Provenzas analysis of the data showed that the strategy did pick out brain-signal patterns potentially linked to OCD symptom fluctuation. While more work needs to be done across a larger cohort, this initial study shows that this technique is a promising way forward in confirming candidate biomarkers of OCD. we demonstrated the utility of at-home data collection for biomarker identification by observing correlations between spectral power and self-reported OCD symptom intensity.

We were able to collect a far richer dataset than has been collected before, and we found some tantalizing trends that wed like to explore in a larger cohort of patients, Borton said. Now we know that we have the toolset to nail down control signals that could be used to adjust stimulation level according to peoples symptoms.

Once those biomarkers are positively identified, they could then be used in an adaptive DBS system. Currently, DBS systems employ a constant level of stimulation, which can be adjusted by a clinician at clinical visits. Adaptive DBS systems, in contrast, would stimulate and record brain activity and behavior continuously without the need to attend clinic. When the system detects signals associated with an increase in symptom severity, it could ramp up stimulation to potentially provide additional relief. Likewise, stimulation could be toned down when symptoms abate. Such a system could potentially improve DBS therapy while reducing side effects.

Work on this line of research is ongoing. Because OCD is a complex disorder than manifests itself in highly variable ways across patients, the team hopes to expand the number of participants to capture more of that variability. They seek to identify a fuller set of OCD biomarkers that could be used to guide adaptive DBS systems. Once those biomarkers are in place, the team hopes to work with device makers to implement their DBS devices.

Our goal is to understand what those brain recordings are telling us and to train the device to recognize certain patterns associated with specific symptoms, Sheth said. The better we understand the neural signatures of health and disease, the greater our chances of using DBS to successfully treat challenging brain disorders like OCD. As the authors concluded, This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders, the author concluded. The platform presented here lays the groundwork for future transformational studies reliant on ecological neural and behavioral monitoring and assessment of neuropsychiatric illness.

Read more from the original source:
Electrical and Behavioral Signals in OCD Could Guide Adaptive Therapy - Genetic Engineering & Biotechnology News