Category Archives: Human Genetic Engineering

The "Therapeutic Proteins Global Market Report 2020" report has been added to ResearchAndMarkets.com's offering.

The global therapeutic proteins market was valued at about $93.14 billion in 2018 and is expected to grow to $172.87 billion at a CAGR of 16.7% through 2022.

The therapeutic proteins market consists of sales of therapeutic proteins. Therapeutic proteins provide important therapies for diseases such as diabetes, cancer, infectious diseases, hemophilia, and anemia.

Advance technologies for protein-based drug development drives the therapeutic proteins market. Therapeutic proteins cannot be synthesized chemically, they need to be produced by genetic engineering and recombinant DNA technology in living cells or organisms.

Protein-engineering platform technologies such as glycoengineering, pegylation, Fc-fusion, albumin fusion, albumin drug conjugation help to increase the production yield, product purity, circulating half-life, targeting, and functionality of therapeutic protein drugs. Belimumab, ipilimumab, taliglucerase alfa, albiglutide, coagulation factor IX recombinant human are some therapeutic protein drugs developed using protein engineering technologies approved by FDA in the past five years.

Increasing biosimilar drugs in global market decline the growth of the therapeutic proteins market. Patent expiry of therapeutic proteins such as monoclonal antibodies give space for entry of biosimilar. In EU, AbbVie evidenced patent expiration of Humira (adalimumab) in 2018, five biosimilar of Humira from Mylan, Amgen, Sandoz, Samsung Bioepis received drug approvals from European commission to enter the EU market. These cost-effective treatments similar to original biologics decline the revenue and sales of therapeutic proteins.

Monoclonal antibody drug approvals are increasing in the protein therapeutic segment. Chronic diseases such as cancer, immunological disorders are well treated with monoclonal antibodies. Monoclonal antibodies are dominant and well-established product class in the protein therapeutic segment with more safety and immunogenicity than antibodies.

Cell-based expression systems such as Chinese hamster ovary (CHO) mammalian cell expression system with latest technologies increased the productivity of monoclonal antibodies by overcoming the problems associated with earlier antibody drugs. In last five years, FDA approved 213 drugs, among them 44 are monoclonal antibodies. In 2018, twelve monoclonal antibodies were approved by FDA for the treatment of cancer and immunological disorders.

In the United States, therapeutic protein drug manufacturers file therapeutic biologics application (BLA) to FDA for the product approvals. The drug approved through BLA should be proved as safe, pure and potent. FDA consolidated review of most therapeutic proteins in Center for Drug Evaluation and Research (CDER). In European Union, biologics are regulated by Committee for Medicinal Products for Human Use (CHMP) for marketing authorization.

In June 2018, Sanofi, a therapeutic solutions provider acquired Ablynx for $4.8 billion. With this acquisition, Sanofi strengthen its R&D strategy with the addition of Ablynx's nanobody technology platform. Sanofi will also focus on technologies addressing multiple disease targets with single multi-specific molecules. Ablynx, a biopharmaceutical company based in Ghent, Belgium, that develops proprietary therapeutic proteins based on single-domain antibody fragments.

Major players in the market are Abbott Laboratories, Amgen Inc., Baxter International Inc., Eli Lilly and Company, F. Hoffmann-La Roche Ltd

Other Companies Mentioned

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Global Therapeutic Proteins Market Report 2020: Market was Valued at $93.14 Billion in 2018 and is Expected to Grow to $172.87 Billion through 2022 -...

The 2010s saw breakthroughs in medical science and spectacular discoveries in space and physics. For Californians, it was also the decade that climate change arrived in our front yards in the form of serial cataclysmic fire seasons.

During the decade, scientists refined the regimen of HIV/AIDS medication, made life-saving advances in the treatment of cancer, and invented an entirely new gene-editing technology, with the hope of one day curing diseases before they begin.

NASAs New Horizons probe captured the first close-up images of Pluto, and the world caught its first glimpse, albeit a bit blurry, of a black hole. Our understanding of exoplanets exploded: the Kepler Space Telescope and the TESS satellite found thousands of new planets outside our solar system, and researchers began to comprehend what those worlds might actually look like.

As the decade closes, the KQED Science team has created a sort of mixtape of the major trends, significant moments and noteworthy discoveries, with an eye toward California and the Bay Area.

Do you want the good news or the bad news first? Well, lets get it out of the way ...

Wildfires Create Havoc

The changing climate is leading to longer dry periods in California, which is at least three degrees warmer since the beginning of the industrial era, the Environmental Protection Agency reported in 2016.

Climate change, combined with a century of suppressing wildfires and denser populations in areas perilously close to fire-prone wilderness, have created the worst fire seasons on record. Since 2012, four of the five biggest California wildfires have burned over 1.2 million acres.

Late on Oct. 8, 2017, hot, dry winds downed power lines, carrying sparks and flaming embers long distances to ignite multiple fires. The Tubbs Fire and other North Bay blazes scorched large areas of Sonoma and Napa counties, claiming 44 lives and destroying over 8,000 buildings.

The following summer, during the Carr Fire, a "fire tornado" exploded into the outskirts of Redding, devastating everything in its path. The blaze killed eight people and destroyed 1,000 homes.

But the worst was yet to come. In November, the Camp Fire nearly wiped out the town of Paradise and surrounding communities. It was the deadliest wildfire in California history, killing 86 people, destroying almost 14,000 homes, and costing more money than any natural disaster in the world that year. Across wide swaths of the state, smoke from the fire rendered the air unhealthy to breathe, inundating the Bay Area for almost two weeks so that the region registered its worst air quality on record.

As far as global warming goes, the outlook is not good, whether it relates to fires or to other natural disasters. The 2010s included the hottest year (2017) and the hottest month (July 2019) on record, and the 10 years that make up the decade will almost certainly set a new temperature mark as well, according to the U.N., based on millions of global measurements taken over the last 170 years.

This summer, our series Living With Wildfire: California Reimagined asked some big questions about how the state can, in our warming world, learn to survive more frequent and ferocious conflagrations. Are some fire-prone areas now too dangerous to accommodate new housing? How can towns prepare for mass evacuations? And neighborhoods make themselves fire-resistant? Are Californians willing to suffer the inconvenience and financial cost to protect the state from extreme wildfires? Perhaps, but it will mean big changes in how we think and live. -- Danielle Venton

Rise of Renewables

As Californians began to experience climate change in the form of hotter days and more destructive fires, state policies to mitigate global warming began to pay dividends. Californias investor-owned utilities shattered renewable energy targets mandated by the state, and California reduced its overall emissions of greenhouse gases below the 1990 level, two years ahead of schedule.

These climate policies, in a state with the world's fifth largest economy, helped spur a rapid decline in the cost of renewable energy around the U.S. This past decade, the cost of wind energy fell by 57%, utility-scale solar power by 86%, and battery energy storage by 76%. In 2019, for the first time, power generation in the U.S. from renewable energy surpassed power produced from coal.

Those are big successes, but California has a lot of work to do over the next 10 years if the state is going to meet its 2045 goal of net-zero emissions, also called carbon neutrality. California is way behind in meeting this ambitious objective, in part because emissions from the transportation sector are soaring, due to Californians driving more miles in larger, gas-guzzling trucks and of SUVs.

The state is trying to reverse this trend by incentivizing fuel-efficient cars and setting a target of 5 million electric vehicles traversing California roads by 2030. But meeting that goal is going to be tough, with sales of EVs currently standing at only a fraction of that total.

Meanwhile, frustrated by the lack of progress in the fight against climate change, young people took to the streets the last couple of years. The Sunrise Movement, Youth vs. Apocalypse and other Bay Area advocacy groups participated in global climate strikes protesting the failure of government, finance, industry and other institutions to address climate change.-- Kevin Stark

Medical Advances

The decade saw major advances in the treatment of HIV and cancer.

Over the last 10 years, scientists have perfected antiretroviral drugs, taken daily in a single pill by people who are HIV-positive. These drugs allow HIV patients to live relatively free of sickness, a far cry from the first decade of the epidemic, when the diagnosis was tantamount to a death sentence. No longer highly toxic, antiretrovirals now work so well they can lower a patient's viral load to undetectable levels, making it untransmittable from one person to another. Another daily pill, called PrEP, can be used as a prophylactic against HIV exposure by people who are still free of the virus. Such major strides in treatment and prevention are why scientists are optimistic HIV will be eradicated altogether within the next decade.

For some types of cancer, a treatment called immunotherapy drastically improved survival and cure rates. For example, stage 4 melanoma , which doesn't respond to radiation or chemotherapy, used to mean certain death, with patients surviving less than a year on average. But over the last decade, instead of burning or poisoning cancer cells to stop the disease, new medicines have unleashed the body's natural defenses.

Normally the immune system recognizes disease-causing organisms. But cancer cells go undetected as harmful. New drugs, as well as genetic engineering techniques, make them visible and ripe for attack. Think of it like affixing a flag with the message kill me" on cells that previously operated with impunity. Pancreatic, breast and prostate cancer, among other types, do not currently respond to immunotherapy, but scientists foresee a day when the treatment could be the primary weapon against an array of cancers.

There may also be a day when doctors can eliminate genetic diseases altogether. A tool called CRISPR acts as a molecular scalpel that can make precise changes to genetic mutations giving rise to disease. Scientists hope to one day cure genetic conditions like blindness or sickle cell anemia before they even start. Though tinkering with our DNA raises all kinds of ethical questions about "playing God."-- Lesley McClurg

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The Big Science and Environment Stories of the Decade - KQED

When I first heard about JBS Haldane years ago, I only knew about the final act of his life: that he was a British biologist who moved to India, became a citizen there and died there in 1964. Even that sliver of detail was intriguing. Scientists usually moved from India to the West. What prompted this man to travel in the reverse direction?

Four years ago, I started to examine his life in more detail and grew steadily more fascinated. Here was a man who, as a boy, was often a guinea pig for his scientist father; who wrote his first scientific paper when he was in the trenches during the First World War; who went repeatedly to Spain to help fight Francisco Francos fascist forces; who ruined his body in experiments for Britain's Royal Navy during the Second World War; who got into constant tussles with every kind of authority figure; and who wrote reams of elegant essays on science for the lay reader.

But where Haldane really spoke to me, across the years, was in his astute thinking about how science and politics intersect. Over the past few decades, we have lived in a time when scientific objectivity is often confused for apolitical neutrality. Climate change aside, scientists hardly ever took political stances, or expressed their views on matters of ideology, or occupied the sphere of the public-interest intellectual.

This was not always the case, though. In the first half of the 20th century, during Haldanes time, scientists were vociferous about their politics and their stances on social issues Haldanes own voice the loudest of them all. He decried imperialism and exploitative capitalism. He criticised British and American government policies. He never made a secret of his radical politics and eventually became a card-carrying member of the British Communist Party.

His own scientific field genetics was perhaps the most politicised area of study in his time, and he recognised that. Even while the fundamentals of genetics were being established, the West fretted about their implications. Britain and America worried that the white race was being diluted because the feeble-minded and feeble-bodied were allowed to reproduce, or because immigrants and people of colour were having children with white men and women. The state machinery moved to prevent this. In Britain, about 65,000 people were segregated because they were considered unfit to reproduce. In America, an equal number of people were sterilised.

Haldane lambasted these measures, calling them not only unethical but also unscientific. Similarly, when Nazi Germany formulated racial purity laws and marched towards ethnic cleansing, Haldane excoriated that false science as well. The Nazi doctrine of "blut und boden" blood and soil was rubbish, he wrote witheringly. The only way blood differed was in its basic groups A, B, O and AB so the characteristic of a race is not membership of a particular blood group". And none of the soils of Germany were unique to it, he added. Friesland is not unlike northern Holland, Brandenburg is like western Poland.

Race was not a meaningful category in any sense, Haldane argued. The genes of people can vary more within a so-called race than between two racial groups a fact science has repeatedly confirmed

Like other members of his class and nation, Haldane grew up believing that some races were inferior to others. But as genetics progressed and its implications became clearer, he changed his views. Race was not a meaningful category in any sense, he argued. In fact, the genes of people can vary more within a so-called race than between two racial groups, he wrote a fact that science has repeatedly confirmed.

In his most famous essay, Daedalus, Haldane warned that as humanity refines its skills to manipulate its own genes, it will have to construct a new morality to deal with these powers responsibly. He recognised a fundamental truth: genetics is the science of differences and with such a science, the invasion of politics is inevitable.

Haldanes ideas ring with increased urgency today. All around us, we see the rise of identity politics of an exclusionary politics based on who belongs, or does not belong, to a nation. Who should or should not cross a border. Who should or should not be thought of as a citizen.

In India, Haldanes adopted home, the government has just passed a bill to expedite the citizenship process for refugees fleeing religious persecution from three of its neighbouring countries. Refugees of every faith except Islam have been promised a quick track to citizenship. The signal is loud and clear: Muslims do not belong here.

Around the world, communities and groups have come to believe that they are distinct, or special, or superior, even though science emphasises that this is false

Echoes of this are everywhere. In China, Uighurs are being segregated. In America, the president wants to build a wall to keep out Mexican and South American immigrants and refugees. In Britain, a narrative that the country should turn inward rather than ally itself with a larger union has conclusively won. There is sectarian strife in Lebanon and Iraq, and white nationalism in Europe. Around the world, communities and groups have come to believe that they are distinct, or special, or superior, even though science emphasises that this is false.

Toss genetic engineering into this mix and things only get more incendiary. Haldane was unequivocal in his belief that the social differences of class need to be stripped away. But at the moment, the danger is that if and when scientists figure out how to re-tailor the human genome, the rich will first buy themselves better genes. The inequalities of wealth will be compounded by new inequalities of ability and physiology. If we are not cautious, the gaps in human society will yawn wider and wider.

At a time like this, Haldanes life and work offer us plenty of guidance. He urged his readers and his students to adopt the scientists perspective of sceptical rationality: to question authority, to demand proof for received wisdom, to make decisions based on evidence.

But Haldane was not a proponent of scientism; he did not believe that peace and progress could be delivered exclusively through science.Haldanes university degree was in the classics, not in biology or chemistry or any other scientific discipline, and he always saw his field with the eyes of a humanist who had wandered into it.

He believed, therefore, that we have to consider our societys frailties and foibles, even as we decide what to do with new science and technology. We have to find ways to live with each other before we discover how science can best improve the human condition. And this is an urgent task. The march of science does not wait for us to grow mature enough to know how to use it wisely. He believed, therefore, that we have to consider our societys frailties and foibles, even as we decide what to do with new science and technology.

Haldane was, in his country and in his time, one of the most famous scientists around perhaps even as well-known as Einstein, and certainly the most politically vocal in his profession. Since then, he has sunk somewhat into obscurity. The 21st century, though, is an appropriate time to remember him and through his work, to rediscover lessons for our own age.

Samanth Subramanian is a regular contributor for The National. His latest book is titled A Dominant Character: The Radical Science and Restless Politics of JBS Haldane

Updated: December 21, 2019 11:17 AM

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The rise of identity politics is a reminder of Haldane's worst fears about genetic manipulation - The National

The concept of using bispecific antibodies for tumor therapy has been developed more than 30 years ago with many initial struggles. However, new developments such as sophisticated molecular design and genetic engineering have helped tremendously in solving many technical challenges and created the next generation bispecific antibodies with high efficacy and safety profiles.

With many successes recently, the zoo of bispecific antibodies now consists of more than 100 different formats, and about 80 bispecific antibodies are currently in clinical trials.

KEYNOTE PRESENTATION: Current Landscape and Outlook of Bispecific Antibody

Roland Kontermann, PhD, Professor, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart

Bispecific antibodies have experienced a dramatic interest and growth for therapeutic applications, with more than 80 molecules in clinical development; e.g., in oncology, immuno-oncology, but also for non-oncology applications. An overview will be given on the making of bispecific antibodies and the various therapeutic concepts and applications, e.g., for dual targeting strategies, retargeting of immune effector cells, and substitution therapy by mimicking the function of natural proteins.

Functional Screening Unlocks the Therapeutic Potential of Bispecific Antibodies

Mark Throsby, PhD, CSO, Merus NV

Case studies of clinical assets will be discussed that highlight the role of empirical functional screening. Examples will include both I-O and targeted therapies demonstrating that diverse functional readouts can be incorporated into bispecific antibodies screens.

Selection-Based Development of a Heavy Chain-Light Chain Pairing Technology

Paul Widboom, PhD, Associate Director, Antibody Discovery, Adimab LLC

A significant challenge in the development of multivalent bispecific antibodies involves solving the heavy chain-light chain pairing problem. While most heavy chain-light chain pairs possess a preference for their cognate partner, noncognate mispairing occurs. Avoiding these undesired mispairs is a relevant challenge in the field of bispecific antibody manufacturing. Here we present a solution to the heavy chain-light chain problem derived from a novel selection system. This system finds mutations that improve cognate heavy chain-light chain pairing while maintaining antigen binding affinity.

A Novel Class of Fully Human Co-Stimulatory Bispecific Antibodies for Cancer Immunotherapy

Dimitris Skokos, PhD, Director, Immunity & Inflammation, Regeneron Pharmaceuticals

T-cell activation is initiated upon binding of the T-cell receptor (TCR)/CD3 complex to peptide-MHC complexes (signal 1); activation is then enhanced by engagement of a second co-stimulatory receptor, such as the CD28 receptor on T cells binding to its cognate ligand(s) on the target cell (signal 2). Recently described CD3-based bispecific antibodies act by replacing conventional signal 1, linking T cells to tumor cells by binding a tumor-specific antigen (TSA) with one arm of the bispecific, and bridging to TCR/CD3 with the other.

Next-Generation Bispecifics for Cancer Immunotherapy

Michelle Morrow, PhD, Vice President, Preclinical Translational Pharmacology, F-star

The use of bispecific antibodies can potentially modulate anti-tumour immune responses. Bispecific antibodies: an attractive alternative to cancer treatment combinations. F-stars approach to create bispecific mAb. In vitro and in vivo efficacy of F-star bispecific antibodies targeting oncology pathways observed in preclinical studies.

Bispecific Gamma Delta T Cell Engagers for Cancer Immunotherapy

Hans van der Vliet, MD, PhD, CSO, LAVA Therapeutics; Medical Oncologist, Amsterdam UMC

V9V2 T cells constitute the largest T cell subset in human peripheral blood and are powerful anti-tumor immune effector cells that can be identified in many different tumor types. This presentation will discuss bispecific antibodies designed to engage V9V2 T cells and their use for cancer immunotherapy.

Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy

Eric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals

This presentation will describe Regenerons bispecific platform and present preclinical data on REGN4018, a clinical stage T cell engaging bispecific targeting Muc16 for solid tumor indications. In addition, status updates on Regenerons other clinical stage bispecific antibodies (REGN1979, REGN5458, REGN5678) will be presented as well as a discussion of new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy.

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Advances in Bispecific Antibody Development are Leading to an Evolution in Anti-cancer Drugs - OncoZine

2019 was nuts for neuroscience. I said this last year too, but thats the nature of accelerating technologies: the advances just keep coming.

Therere the theoretical showdowns: a mano a mano battle of where consciousness arises in the brain, wildly creative theories of why our brains are so powerful, and the first complete brain wiring diagram of any species. This year also saw the the birth of hybrid brain atlases that seek to interrogate brain function from multiple levelsgenetic, molecular, and wiring, synthesizing individual maps into multiple comprehensive layers.

Brain organoids also had a wild year. These lab-grown nuggets of brain tissue, not much larger than a lentil, sparked with activity similar to preterm babies, made isolated muscles twitch, and can now be cloned into armies of near-identical siblings for experimentationprompting a new round of debate on whether theyll ever gain consciousness.

Then of course, theres the boom in neurotech. Fostered by insight into how neurons and circuits communicate with each other through a complex neural code, weve gotten ever closer to decoding the brain. Mind-controlled prosthetics are old news; the frontier now is engineering robotic limbs that can truly feel. Insight into our sensory cortices are inspiring light-based nervous systems that give robots multitudes of sensations. Elon Musks Neuralink finally came out after years of speculation, and a Wild West of brain-computer interfaces have sprung up, with the hope of one day restoring broken brain circuits without the need for surgery.

Thats already achievement-a-plenty. But as we wrap up the year, there are four mind-bending stories that still stick with meby asking about the nature of death, the promise of mind-reading, and new paths that may finally help us beat Alzheimers. These are the ones Ill leave you with.

The brain is a powerful but ultra-sensitive organ thats prone to injury. Once deprived of oxygen and nutrients, cells can begin to die within the hour. Thats why, zombie lore aside, scientists once thought its near impossible to resuscitate a brain to any sort of function hours after death.

Not true. In April, a team at Yale University reported that they successfully detected electrical activity in pig brains four hours after death. The results were a surprise: the team originally set out to develop a system that helps the brain maintain its integrity after removal for experimental purposes. How well it worked went beyond the teams expectations. Its impossible to say if the brains were conscious; that is, whether they were aware of being revived, though its highly (and I mean highly) unlikely. When the team saw signs of widespread, coordinated electrical activitywhich underlies consciousnessin their initial experiments, they anesthetized future experimental brains to block this sort of united firing, drastically reducing the chance consciousness could emerge in these brains.

Nevertheless, the study suggests that the brain is much more resilient to injuries such as stroke or trauma than previously thought. In the long term, it asks whether we might one day have a sort of CPR for the brain. And if so, how long can brains maintain their health after being separated from the body? We might have just taken the first step into the uncharted territories of death.

A few years ago, Dr. Miguel Nicolelis linked up animals brains into an internet that allowed each member to work collaboratively on a common problem. When connected to each other through implanted electrodes, the animals synced up their brains electrical activity in a way reminiscent of a single hive brain.

Nicolelis has now done the same experiment in humans, minus surgery. In a feat of neural engineering, the team used non-invasive electroencephalographs (EEGs) to read brain waves from two individuals and sent these signals to a third person by zapping their brain with magnetic pulsesa technology called transcranial magnetic stimulation, or TMS. Together, five triad groups solved a Tetris-like game using their brain waves alone, with an accuracy of over 80 percent, even when the researchers introduced noise.

One caveat: the system was rigged so that the neurotech wasnt detecting thought, for example, rotate the block or dont rotate. That decision was encoded as the presence or absence of light flashes, which are much easier for the EEG to read and for the TMS to deliver to the visual cortex. But its still a powerful proof-of-concept, in that even with our rudimentary brain reading and writing tech, its possible to link up human minds into a hive mind to solve problems. Nicolelis imagines a biological supercomputer made from networked human brains, which could conceivably cross language barriers and even enhance cognitive performance. The question is, if we open the sanctuary of our minds to others for gains in computing power, what do we stand to lose in privacy and autonomy?

Playing a collaborative game of Tetris isnt the only way scientists advanced mind reading technology. In January, one team combined deep learning with speech synthesis technology to translate what a person is hearing into reconstructed speech. The system captured electrical signals from the auditory cortex while a person listened to recordings of people speaking. These activity patterns were then decoded by an AI-based speech synthesizer and produced intelligible, if somewhat robotic, speech. Unfortunately, the system couldnt decode someones own internal thoughts.

But that changed three months later.

Another team engineered a neural decoder that decodes electrical signals measured from the cortex, the outermost layer of the brain. Rather than containing information about semantics, these signals represent movement of the lips, tongue, larynx, and jaw. Different movement patterns are associated with different sounds, which the decoder can identify and synthesize into actual comprehensible sentences. For the first time, its possible to know what someone is trying to say by reading their brain activity alone, and the tech was further validated in a Q&A conversation. Earlier this month, yet another team found its possible to decode words and syllables based on recordings from the brains motor cortexthe part usually responsible for hand and arm movements. This opens another avenue of reading speech directly from the brain.

Not to be outdone, a team at Russian firm Neurobotics found they could use AI to decode what video clips people are watching based on their brainwaves alone. In contrast to the speech-decoding studies, which use implanted electrodes, here non-invasive EEG was sufficient to reconstruct nature scenes, sports, and human faces.

For now, our private thoughts are still private, and the tech mainly helps those who cant speak reconnect with the world. But think about this: if someday a tech giant offers you the ability to text or post using your mind only, would (and should) you go for it?

Dementia is one of the most frustrating neurological disorders of our time. Despite decades of research, nearly every single Alzheimers drug that targets toxic protein clumpscalled beta-amyloidthought responsible for the disease has failed. Generally, these drugs are proteins that break up clumps or neutralize their toxic effects.

This year saw an explosion in alternative potential treatments and theories.

One that especially gained steam suggests flashing lights and clicking sound could potentially break up toxic protein clumps and improve brain function, at least in mice. The treatment, cheap, non-invasive, and dramatically effective, offers new hope to the long-struggling field. Others suggest that mutations to DNA in brain cells scrambles certain genes and could be a root cause. Yet others are taking a gene therapy approach to the Alzheimers dilemma, adding in a dose of a protective gene variant in high-risk individuals.

Although its impossible to say if any of these new routes will lead anywhere, one thing is clear: the more scientific treatment ideas we have, the higher the chance well finally tame Alzheimers in the near future.

Image Credit: Gerd Altman / Pixabay

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This Year's 4 Most Mind-Boggling Stories About the Brain - Singularity Hub

We can already edit genes in human embryos. We can even do it in a way to pass the edits down generations, fundamentally changing a familys genetic makeup.

Doing it well, however, is far more difficult.

Its impossible to talk about human germline genome editing without bringing up the CRISPR baby fiasco. Over a year ago, a rogue Chinese scientist performed an edit on fertilized human embryos that, in theory, makes them resistant to HIV infection. Two twin girls were born, and both had multiple unplanned edits in their genome with unknown health consequencesconsequences that may be passed on to their offspring.

The brash attempt at making scientific history clearly shows that, ethics and morality issues aside, when it comes to germline editingthat is, performing gene edits in egg, sperm, or the embryowere simply technologically not there. Make no mistake: CRISPR may one day wipe out devastating genetic diseases throughout entire family lines, or even the human race. But to harness its power responsibly, there are plenty of technical challenges we need to master first.

This week, Rebecca Lea and Dr. Kathy Niakan at the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute in London, UK, laid out those challenges in a sweeping articlein Nature. CRISPR as a gene editor is getting more specific and efficient by the day, they explained. However, for it to gradually move into germline editing, we also need to understand how the tool tangos with cells during early human development.

The data, they argue, will not only let us zoom into the creation of human life. It will also help inform the debate about potential safe and effective clinical uses of this technology, and truly unlock the doors to the human genome for good.

Correcting dangerous genetic mutations is one reason to pursue germline editing, but CRISPRing human embryos can also unveil insights into the very first stages of human embryo development. Research shows that trying to understand how human embryos form by studying mice might not be the best route, especially when it comes to using those results to tackle infertility and other medical problems. With CRISPR, we have insight into these early stages that were previously completely unattainable. We might only solve infertility issues, but perhaps also allow same-sex couples to have genetic children in the future.

Another argument is that couples already screen for life-threatening mutations during IVF, and using CRISPR on top of that is unnecessary. Not true, the authors argued. When both parents carry a similar mutation that robs them of the ability to have a healthy child, CRISPRnot selection during IVFis the answer. Ultimately, providing more options for patients empowers them to make the choice that is best for their family and circumstances, they said.

This is where it gets complicated.

The big one: were still trying to tease out how CRISPR works in cells that form the embryo, in hopes that we can cut down on potential mistakes.

Let me explain: all cells in the body have a cell cycle, somewhat analogous to a persons life cycle. Many checkpoint life events happen along the way. The cell could decide to divide and have kids, so to speak, or temporarily halt its cycle and stop its own aging. During a cycle, the cells DNA dramatically changes in number and packaging in preparation for its next stage in life.

The problem? The way CRISPR works heavily depends on the cell cycle. Although dubbed an editor, CRISPR actually vandalizes the genome, creating breaks in the DNA strands. What we call gene editing is the cells DNA repair system kicking into high gear, trying to patch up the mess CRISPR left behind. Adult cells that cant be repaired stop their own life cycle at a checkpoint for the greater good. In embryos, however, cells arent nearly as altruistic. Their checkpoints arent fully developed, so they might continue to develop even with severe mutations. Zooming back to the full picture, it means that the resulting early-stage embryo may keep accumulating damage, until it fails in the mothers womb.

To get around this, scientists have tried other ways to push an embryo into accepting a healthy DNA template after a CRISPR snip, which in theory would cut down on unwanted mutations. One idea is injecting the CRISPR machinery at a specific time into fertilized eggs, so it catches the early-stage embryo at just the right time to reduce DNA breaks in both strands. While theoretically possible, the process is kind of like a person trying to jump from a high-speed train into a specific cabin on a rapidly rotating Ferris wheel while blindfolded.

But science is making progress. Although we dont have a detailed movie of cell cycles in human embryos yet, multiple labs are beginning to piece one together, with hopes itll eventually help take off the blindfold when injecting CRISPR. Others are looking into adding CRISPR to sperm before fertilization as an alternative.

At the same time, scientists are also trying to characterize the entire scope of mutations caused by CRISPR. Its not just adding, swapping, or deleting specific letters in genes. Rather, the range of mutations is more complex, including large swaths of genetic rearrangements, unintended cuts relatively far from targeted spots, and other dramatic DNA lesions following CRISPR action. Its perhaps not surprising that the edits in CRISPR babies didnt work as intended.

Base editors, which swap one genetic letter for another, might be a better approach compared to the classic hack-and-paste, the authors said. So far, however, the tools havent yet been validated in embryosnot even those from mice.

Finally, for the edit to make a difference to the child, the embryo has to develop normally inside a womb into a baby. But success rates for assisted reproductive technologies are already fairly low. Add in a dose of genetic editing tool that cuts into an already-sensitive genomic landscape, and it becomes incredibly hard to maintain the health of the edited embryo.

Putting it all together, there is simply not enough data at present to understand the capability of early[embryos] to repair DNA, the authors said.

Far from it. Although theres much we dont yet understand, we do have an impressive range of tools to predict and evaluate mutations in human embryos. Exactly how to determine whether a gene-edited embryo is healthy remains up for debatefor example, is five unexpected mutations considered ok? What about 500 or 5,000?

That said, just having tools to diagnose the genetic health of an embryo from a tiny bit of DNA is already extremely useful, especially if we as a society decide to move into germline editing as a treatment.

With machine learning making an ever-larger splash in computational biology, these predictive tools will only become more accurate. Add to that ever-more-effective CRISPR variations, and were on the right trackas long as any potential applications of embryo editing only come after in-depth public and policy discussions and fit a number of strict ethical and safety criteria, the authors said.

In response to the CRISPR baby scandal, multiple governments and the World Health Organization have all drafted new guidelines or legislation to tap on the brakes. The technology isnt mature enough for clinical use, the authors said, and much more work is needednot just to further improve CRISPR tools, but especially for understanding how it works in human embryos.

Ultimately, were talking about potentially engineering the future of the human race. Tiptoeing, rather than stumbling ahead, is the least we can do. One must ensure that the outcome will be the birth of healthy, disease-free children, without any potential long-term complications, the authors concluded.

Image Credit: Image by marian anbu juwan from Pixabay

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How Far Are We from (Accurately and Safely) Editing Human Embryos? - Singularity Hub