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Category Archives: Human Genetic Engineering

50 inventions you might not know were funded by the US government – WFMZ Allentown

Its no secret that the United States government has played a huge role in the creation of major technological and medical breakthroughs over the past few hundred years, but did you know that its responsible for many of the devices and products that many people use every day?

If youve ever used a GPS system, you have the Defense Departments research to thank. What about your smartphone? Although the government didnt directly fund the exact phone you own, NASA, the National Science Foundation (NSF), and the CIA were integral in creating crucial elements of todays smartphonessuch as microchips and touch screens. Even the internet, which makes reading this story possible, began as the Advanced Research Projects Agency Network (ARPANET), a computer network first made by the U.S. Defense Advanced Research Projects Agency (DARPA).

Perhaps one of the most consequential fieldsthat hasbenefited most crucially from government support is that of medicine. Many vaccines that prevent millions of Americans from contracting preventable diseasesfrom the common flu to Haemophilus influenzae type Bwere funded and developed with support from the National Institutes of Health (NIH). More recently, the federal initiative Operation Warp Speed was established to facilitate the manufacture and distribution of the coronavirus vaccines.

However, government research and funding have been integral to so many inventions, big and small, that it can be hard to find a starting point when learning about which ones can be credited to various supporting agencies. Stacker compiled information about government-funded creations using a combination of news, scientific, and government reports. The inventions on this list encompass a wide variety of areas, including technology, agriculture, medicine, aviation, and others.

From the beginnings of the civilian aviation industry in 1925 to a recent COVID-19 vaccine breakthrough in 2020, read on to learn about 50 inventions you might not know were funded by the U.S. government.

You may also like: 25 IPOs that bombed on their first day

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How Tech Trends Among Runners Help Us Envision the Future of Athletics and Society – Built In

The rapid progression of science and technology is converging with societal, economic, environmental and geopolitical shifts in ways that alter our future. As a result, people everywhere are focused on the future of X, where X increasingly represents every domain.

It is not surprising then to see the future of sports impacted by this convergence. There is no doubt that the future of sports and running in particular is changing. Tata Consultancy Services (TCS) launched #ThisRun, a new worldwide community for runners, reinforcing its long-standing commitment to global marathon and running partnership platforms. In support of this initiative, TCS conducted This Run Tech Survey, which captured runners views of technology and its role in the sport now and in the future. It provides a glimpse into the minds of a broad spectrum of runners, giving us foresight to see across horizons. With it, we can envision the future of running and explore how it may impact societal wellness.

Every analysis of future scenarios now includes the impact of COVID-19, and running is no exception. Our survey indicates that running has sparked more enjoyment and importance in the pandemic-filled lives of people. In fact, 67 percent of respondents said that running during the pandemic has been especially important in their life. With stress and depression amplified, running has reduced some of those worries. While the pandemic has been one key motivator, technology adoption represents another. Currently, running technology is used to track fundamental metrics such as pace, distance and time. The focus is primarily on individual runners connecting, capturing and leveraging data and technologies to improve their experience and performance. The survey indicates that runners are interested in practical uses of running-based technologies, with respondents interested in injury prevention (59 percent), runner performance (58 percent) and nutrition/hydration (58 percent).

Popular technology includes smart watches, distance tracking apps and heart-rate monitors. Our survey highlights several other technologies embraced by both avid and casual runners. The early adopter nature of runners creates a virtuous cycle, where technologies are adopted at a faster rate, thus accelerating product innovation and product demand. COVID-19 has amplified this virtuous cycle, as it has in many different domains. As the cycle continues, a broader lens illuminates the potential role that technology will play in the future of running (or any sport). Imagine how we might maximize performance through wearables, game technology, AI coaching, VR tracking, gene doping, neuro-coaching and, ultimately, brain-to-brain communication.

If we pull back our lens even further and envision the future athlete, we can see the total reimagination of sports. We are likely to experience a complete blurring of boundaries between technology and the athlete. Exoskeletons, implants, artificial body parts or human-machine convergence could alter the athlete and therefore the sports themselves. Does this lead to enhanced leagues versus natural leagues? What happens if genetic engineering enables the creation of super athletes or genetic screening allows us to pick only the best children for participation in sports? It is not far-fetched to imagine leagues where robots compete against each other. Now, go even broader. These early indicators from our survey portend a world that is to come. As we look to this future, does the survey provide signals that help envision that future? Two key signals include the environment and wellness.

Our survey found that avid runners are more likely to be motivated by green technology specifically the carbon footprint of races (59 percent of avid runners would be more interested in participating in a carbon-neutral or zero-carbon-footprint race).

From a wellness perspective, a connected health platform emerges to improve the health of athletes and humans more broadly. This connectedness ultimately drives a wellness ecosystem that accrues value to the collective. The ecosystem evolves to support individual needs, while athletes contribute to collective intelligence on wellness. This enables wellness that permeates every aspect of our lives.

Were now able to monitor our health at the cellular level and our environment through the smart home; we enjoy 3D-printed food that meets our individual nutritional needs; our clothing regulates our body temperature based on our internal and ambient temperature; injuries are healed through smart bandages and rapid cell regeneration; and all of our health and wellness data is integrated into an AI-powered dashboard. These metrics improve overall health and wellness, contributing to the extension of healthy lives.

In this era of genomics, precision medicine and rejuvenation biotechnology, extending our healthy lives is not only possible but likely. Life scientists believe that the first person to live to 200 has already been born. When I look at innovation in the health domain and the rapid progression experienced in the last two decades, I see the possibilities. Catalysts like pandemics have always served as both obstacles and accelerants. In the area of health, it is the latter. Imagine the extended athletic careers these advancements may enable. When viewed through the lens of the athlete, a broader view of our emerging future materializes. Enjoy the journey!

Read More Fantastical StoriesThe Incredible, Sci-Fi-Like Future of Blood Testing

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Genetic engineering transformed stem cells into working …

Takeaways

Scientists have made progress growing human liver in the lab.

The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new field called synthetic biology focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals like proteins or sugar in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students Jeremy Velazquez and Ryan LeGraw used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

[Deep knowledge, daily. Sign up for The Conversations newsletter.]

Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile a chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

Mo Ebrahimkhani, Associate Professor of Pathology and Bioengineering, University of Pittsburgh

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Raw Story is independent. You wont find mainstream media bias here. Every reader contribution, whatever the amount, makes a tremendous difference. Invest with us in the future. Make a one-time contribution to Raw Story Investigates, or click here to become a subscriber. Thank you.

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Everything You Need to Know About Genome Editing – Interesting Engineering

Every cell in your body has around 3 billion base pairs of DNA code inside it. Just a few small errors in this code could leave someone with a debilitating illness. Molecular biologist Eric Olsen has described it as equivalent to misspelling one word in a stack of one thousand bibles, and this tiny typo could put a child in a wheelchair for life.

Researchers have already identified DNA errors as the cause of nearly 7,000 diseases. Thankfully, the growing world of genome editing could be the "spell-checker" needed to detect and eventually fix these problems.

Genome editing is often equated with designer babies and CRISPR/Cas9. However, the world of genome editing is far more diverse and complex and goes well beyond just CRISPR, which is only the latest in a long line of editing "tools". Genome engineering is a type of genetic engineering in which DNA is inserted, deleted, modified, or replaced in the genome of a living organism.

It is an incredibly powerful tool with tremendous potential in the field of medicine. In its simplest form, it is a way of making specific changes to the DNA of an organism. It's similar to editing the code in a piece of computer software.

There is a reason why there is a lot of hype around gene editing, and you should be excited too. Genome editing could potentially be used to treat major degenerative diseases and fix simple genetic conditions like muscular dystrophy. It may one day soon be used to grow new human organs in pigs, combat the constant demand for organ transplants, and potentially turn human reproduction on its head, yes, we're talking about using it to engineer entire populations.

We are still a ways away from the movie Gattaca, or Aldous Huxley's Brave New World. Nonetheless, real-world gene engineering poses some very interesting ethical questions. Today we are going to look at the history of genome editing, new methods like CRISPR, as well as alternatives, and look at some of the ethical questions currently plaguing this medical tool.

Okay, to review, genome editing or gene editing is a relatively new method that lets scientists change the DNA from bacteria to animals. These "edits" could potentially lead to changes in physical traits like eye color, or, more importantly, to cure certain diseases. Genome editing has already been used in agriculture to modify crops to improve their yields and increase their resistance to disease and drought.

There are many different methods and technologies used to edit DNA. Nonetheless, most of these technologies generally act like the "cutting" and "pasting" functions on your computer, allowing scientists to alter the DNA at a specific spot in an organisms' genome. Though much of the hype around gene editing centers around its power to engineer humans, the main application of genome editing so far has been in plants and some animals in lab settings.

Once it was realized in the 1940s that DNA was responsible for heredity, and once the structure of the DNA molecule was elucidated in the 1950s,researchers realized that errors in this genetic code were responsible for many diseases and inherited conditions.

The question that followed was an obvious one. Could these errors be corrected? This question led to the emergence of genetic engineering in the 1970s, where new genetic code was introduced into organisms' DNA. However, this technology was not initially capable of inserting the new material in a highly targeted way.

One early example of targeting genes to certain sites within a genome of an organism usedhomologous recombination. This method involves the construction of a sort of template that matched the targeted genome sequence, and relied on the normal cell processes to insert this template at the correct location. The method was successfully used to introduce genetic modifications in mice using embryonic stem cells.

Another early method used conditional targeting using enzymes calledsite-specific recombinases(SSR). These techniques were able toknock out or switch on genes only in certain cells and ultimately allowed researchers to induce recombination under certain conditions, allowing genes to be knocked out or expressed at particular times or at particular stages of development.

The key to genome editing is creating a double-stranded break(DSB) in the genome at a specific point and removing the erroneous part of the genetic code. Enzymes are then used to repair the break, rejoining the ends of the DNA or to insert the missing correct sequences in the correct location. However, while certainenzymes are effective at cutting DNA, they generally cut at several multiple sites - potentially removing DNA that researchers do not want removed. To overcome this challenge, several types of nucleases (enzymes) have been created. These are called Zinc finger nucleases (ZFNs), transcription-activator like effector nucleases (TALEN), meganucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9).

Meganucleases werediscovered in the late 1980s, they canrecognize and cut DNA sequences of between 14 and 40 base pairs. However, it can be difficult to engineer nucleases that will cut the DNA at the exact site needed. Recently, a library of sorts has been created that has allowed scientists to more easily create meganucleases that will cut in specific locations. For example, there are now meganucleases able to remove mutations to the human XPC gene which causeXeroderma pigmentosum, a disorder that predisposes the patients to skin cancer and burns when exposed to UV light.

In the 1990s, scientists used zinc-finger nucleases to improve existing gene-editing techniques. These synthetic proteins are used for gene targeting and are composed of DNA-cutting endonuclease domains fused to zinc finger domains engineered to bind a specific DNA sequence. They can be used to add or delete cut sites in the genomes of cells. Though this method has been dramatically improved, the success rate is still only about 10 percent. Even more so, this gene-editing method is costly and time-consuming to design.

Transcription activator-like effector nucleases (TALEN) share some similarities to Zinc-finger nucleases. Developed in 2009, TALENs are engineered from proteins found in nature and are capable of binding to specific DNA sequences. And while their effectiveness and efficiency parallel ZFN, they are far easier to engineer.

While ZFN and TALEN do offer effective genome editing, one drawback is that they are both time-consuming and expensive to develop. And, the process of engineering proteins is prone to error. CRISPR is so revolutionary in gene editing realms because it offers scientists a faster and simpler way to edit the genome, "with little assembly required." CRISPR/Cas9 was already on the radar of researchers in the 1990s, but its full potential was not realized until recent years.

CRISPR/Cas9 is a powerful new gene-editing technology developed separately in around 2012 by scientists Feng Zhang, Jennifer Doudna, and Emmanuelle Charpentier.

CRISPR can recognize specific genome sequences and cut them often utilizing the Cas9 protein.

CRISPR technology is based on a defense mechanism that bacteria use to fight viruses. Viruses attack cells by using the cells' own machinery to create replicas of themselves. Eventually, the cell bursts and the virus copies are released into the organism to infect new cells. However, bacteria have evolved a way to fight back by cutting up the virus' DNA. If a bacteria survives a virus attack, they copy pieces of that virus' DNA and incorporate these into its own genomes. These copies are used like mugshots to allow the bacteria to identify harmful viruses.

To keep track of this collection of "mugshots" and to keep them separate from the bacteria's own DNA, repetitive sequences of molecules are placed around each sequence that was taken from a virus. When a bacteria comes up against a virus with a sequence in its collection, the bacteria sends an enzyme to cut apart and destroy anything that matches the genetic mugshot. CRISPR allows scientists to use a similar approach, often using the protein Cas9 to cut and replace specific gene sequences.

The CRISPR technique allows scientists to quickly and efficiently alter almost any gene in any plant or animal at a low cost. Researchers already have used the technique to correct genetic diseases in animals, grow crops more resilient to a certain climate, alter pig organs for easier human transplantation, sterilize mosquitos for disease prevention, and add muscle mass to beagles.

Scientists are also able to use CRISPR to create short RNA templates that match a targeted sequence in the genome, making the process of editing far easier, efficient, cheaper, and quicker. CRISPR is currently being used to develop treatments for HIV, Duchenne muscular dystrophy, some types of blindness, and Lyme disease just to name a few.

"CRISPR is incredibly powerful. It has already brought a revolution to the day-to-day life in most laboratories. I am very hopeful that over the next decade gene editing will transition from being a primarily research tool to something that enables new treatments in the clinic,"saidNeville Sanjana, of the New York Genome Center and an assistant professor of biology, neuroscience, and physiology at New York University.

Gene-editingtools like CRISPRcould give scientists the keys to the DNA kingdom, allowing us to find "molecular mistakes" and remove them. According to Nicola Patron, a molecular and synthetic biologist at the Earlham Institute in the UK, "We are getting to a point where we can investigate different combinations of genes, control when, where, and how much they are expressed, and investigate the roles of individual bases of DNA. Understanding what DNA sequences do is what enables us to solve problems in every field of biology from curing human diseases, to growing enough healthy food, to discovering and making new medicines, to understand why some species are going extinct."

Researchers could one day remove malaria from mosquitoes. Researchers have already created mosquitoes that are resistant to malaria by deleting a specific segment of mosquitoes' DNA. Neurodegenerative diseases like Alzheimer's and Parkinson's could potentially become a thing of the past. Scientists are already working on CRISPR-based platforms to identify the genes controlling the cellular processes that lead to neurodegenerative diseases. In 2017, researchers used CRISPR to shut down the HIV virus' ability to replicate, eliminating the HIV virus from infected cells.

In 2016, a lung cancer patient in China became the first human to receive an injection of cells that had been modified using CRISPR. Researchers used CRISPR to disable a gene used by the cancer cells to divide and multiply. Without the gene, researchers hope the cancer cells will not multiply.

From agriculture to pharmaceuticals, gene editing could one day help us build a better world.

Yes and no. Designer babies seem to lead the conversation when discussing CRISPR. Ethical questions like, "Is it okay to use gene therapy on an embryo when it is impossible to get permission from the embryo for treatment?" or "What if gene therapies are too expensive and only wealthy people can access and afford them?" lay at the core of most people's concerns.

What if people use these tools to improve a child's athletic ability or height rather than use it for treating diseases?

Would this lead to genetic discrimination? Though researchers are still navigating the arguments for and against, gene editing in humans has already begun.

The US, China, andthe UKhave approved gene editing in humans for research purposes only.

Even popular gene-editing tools like CRISPR are still not perfect. In some cases, the gene-editing tools make cuts in the wrong places, and researchers are still not 100% sure how that will affect people. Properly addressing the ethical concerns and ensuring gene editing safety are still two massive mountains that scientists need to climb before we see mainstream genome treatments.

In her book, A Crack in Creation: The New Power to Control Evolution,Jennifer A. Doudas paints us a picture of a gene-edited world, stating, "Tomatoes that can sit in the pantry slowly ripening for months without rotting. Plants that can weather climate change better. Mosquitoes that are unable to transmit malaria. Ultra-muscular dogs that make fearsome partners for police and soldiers. Cows that no longer grow horns."

She adds: "These organisms might sound far-fetched, but in fact, they already exist, thanks to gene editing. And they're only the beginning. As I write this, the world around us is being revolutionized by CRISPR, whether we're ready for it or not."

It does not sound too bad, right? What is your opinion on gene-editing? How will it change the world?

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Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease – The Conversation US

Takeaways

Scientists have made progress growing human liver in the lab.

The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new field called synthetic biology focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals like proteins or sugar in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students Jeremy Velazquez and Ryan LeGraw used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

[Deep knowledge, daily. Sign up for The Conversations newsletter.]

Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile a chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

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Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease - The Conversation US

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Multiple gene edits and computer simulations could help treat rare genetic diseases – University of Wisconsin-Madison

The lab of KrisSaha at the University of WisconsinMadison has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders.

In proof-of-concept experiments, the labs researchers efficiently corrected multiple mutations responsible for a rare metabolic disorder, known as Pompe disease, in cells containing the disease-causing errors. They also used computer simulations to design the ideal gene-editing approach for treating human patients, a boon for rare disorders like Pompe disease that lack useful animal models.

Their promising platform advances the CRISPR genome-editing field and could lead to effective treatments for many diseases, not just Pompe disease.

The exact mutations seen in the Pompe patients are not in an existing animal model, so we cannot do all of the preclinical studies that we would like to do in order to evaluate the safety and efficacy of different genome editing strategies, says Saha, a professor of biomedical engineering at UWMadisons Wisconsin Institute for Discovery. We need a way to think about how we go from patient material to a therapy without having to build an animal model, a process that takes months to years and hundreds of thousands of dollars.

The lab of Kris Saha (standing) has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders. Photo: Stephanie Precourt

Sahas team published its findings Dec. 8 in the journal Nature Communications.

In the first few months of life, an infant with Pompe disease becomes weaker and weaker as glycogen builds up in their muscles, their cells unable to break the complex sugar down. Multiple mutations in a gene calledGAAprevent their cells from correctly producing the proteins needed to make lysosomes, which turn glycogen into glucose, the fuel that powers cells. Left untreated, most patients with Pompe die within a year.

Developing effective therapies for such diseases can be difficult for a number of reasons. First, diseases like Pompe have no animal models in which to test treatments, a typical step in therapy development. And diseases like Pompe and many other inherited diseases are autosomal recessive, which means that mutations are present on both copies of a chromosome. Two sets of mutations require two successful gene-repair events for maximum effect. Further complicating the matter is the fact that many diseases are polygenic, resulting from mutations in two or more genes or multiple mutations spread across a single gene, as is the case for Pompe disease.

The Saha labs new approach uses precise gene-editing tools to edit both faulty alleles simultaneously within individual cells to restore function. In its new report, the research team used induced pluripotent stem cells derived from Pompe patients to reproduce the exactGAAmutations that cause the disease and to approximate the resulting tissue pathology.

To fix these Pompe mutations, the lab turned to a specially designed, ultra-precise genome-editing system described in aprevious studyled by Jared Carlson-Stevermer, who was at the time a graduate student in Sahas group. That report established an up to 18-fold increase in precision of gene edits by combining a DNA repair template with the cutting machinery of CRISPR in one particle.

In the current study, the researchers used the method to fix two mutations at once in Pompe-derived cells. By doing so, the researchers improved cell function dramatically, bringing lysosome protein production up to the level of healthy cells without any major adverse effects, which sometimes emerge from gene editing.

The research advances the CRISPR genome-editing field and could lead to effective treatments for many diseases.

But treating cells in the laboratory, while providing crucial insight, is not the same as creating a therapy for patients. A critical step in developing treatments usually involves testing on animal models to evaluate efficacy and safety, a major obstacle for Pompe disease and other genetic conditions that lack viable animal models.

To determine the best therapeutic strategy for polygenic diseases evaluating different doses, delivery mechanisms and timing, risks and other factors the research team instead built a computational model that allows it to predict the outcomes of various conditions.

This allows us to survey a wider scope of many different gene therapies during the design of a strategy, says coauthor Amritava Das, a postdoctoral associate at the Morgridge Institute for Research. The computational approach is critical when you dont have an animal model that resembles the human disease.

After pumping close to a million simulation conditions through the computational model, Das, Carlson-Stevermer and Saha have gained key insights about the delivery of gene editors into the livers of human infants with Pompe disease without having to subject a single patient to experimental treatments. And those insights establish that the multiple-correction genome-editing approach tested in stem cells may be an effective treatment for Pompe and other polygenic recessive disorders.

The computational model, which can be easily adapted for other polygenic conditions, is a big step for the development of therapies for diseases like Pompe and lays the groundwork for a bridge from laboratory studies to the clinic. And as more measurements are added to the model, it will gain more predictive power.

Its a very broad, adaptable platform, Das says about the combined stem cell model and computational tool, and a very different way of thinking about gene therapy.

This work was supported by the National Science Foundation (CBET-1350178, CBET-1645123), the National Institutes of Health (1R35GM119644-01), the Environmental Protection Agency (EPA-G2013 STAR-L1), the University of Wisconsin Carbone Cancer Center (P30 CA014520), the Wisconsin Alumni Research Foundation, and the Wisconsin Institute for Discovery.

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Multiple gene edits and computer simulations could help treat rare genetic diseases - University of Wisconsin-Madison

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