For decades, some unluckydog lovers have welcomeda bundle of barking joy into their homes, only to see them perish from a mysterious disease mere weeks after their birth. The pups seemingly healthy muscles had literally wasted away in front of their owners eyes until they could no longer stand and breathe.

It wasnt until 2010 that a French research team isolated the genetic cause of this specific muscle-wasting disease in a group of Labrador Retrievers; these dogs were suffering from a single mutation that left them unable to produce an essential protein known asmyotubularin.Whats more, it was the exact kind of mutation and disease also long found in male human babies, too. That made the researchers wonder if these unfortunate puppiescould help us study the disease and even someday find a way to saveboth pets and people.

Now, years down the road, it appearsthey were right, thanks to a cutting-edgegene therapy treatment.

An international group of researchers, including some from the original French team, gathered together 10-week-old puppies with the mutation to take part in a randomized controlled trial. The dogs who were given a treatment that repaired their defectivemyotubularingene avoided the crippling muscle degeneration that killed the placebo-treated dogs by week 17. And by the ninth month of study, the saved puppies muscle and neurological function continued to match readings from healthy dogs, particularly forthose that got the highest doses.

The findings, building on an earlier proof-of-concept study of dogs and mice by the researchers, signal that a scaled-up treatment could save the lives of boys with the same sort of genetic flaw.

I believe that the dog study will be about as close as we will ever get to a human study, senior author Dr. Martin Childers of the University of Washington told Vocativ in an email. Because we found evidence that the gene therapy product spread throughout the entire skeletal musculature of adult dogs after a single infusion, it seems reasonable to expect a similar result in human patients.

Gene therapy has received plenty of attention for its potential to treat otherwise irreparable DNA defects, but according to the researchers, theres been little focus on bone- and muscle-relatedgenetic disorders. The condition treated in the current study, called x-linked myotubular myopathy, affects around one in every 50,000 boys, with most sufferers living no more than a few years. And though theres no true tally of how often it affects dogs, case reports of similar-sounding diseases have been published stretching back decades.

There will undoubtedly be hurdles to climb before the treatment Childers and his team developed, or a similar one, can be tested in people, Childers said. It is always possible that humans might respond differently, thus, clinical trials will be conducted with extraordinary care and oversight, he explained. And though the dogs suffered little adverse effects from the therapy delivered via a harmless virus researchers will still have to watch out for any possible toxicity in people.

That said, the treatment offers hope for both man and mutts. The changes seen after a single treatment have lasted for several years in the small sample of dogs the team has raised. So its possible that people wont need repeated doses or they would be infrequent, Childers said a big positive, given how expensive gene therapy is today.

And its also likely that these treatments, within the larger field of regenerative medicine, will find a place for dogs and other animals sooner than it will for people.

Veterinary medicine is ahead of human medicine in some cases with respect to regenerative technologies, Childers said. Stem cell infusions, for example, have been given to pets and horses for more than a decade.

But people may not have to wait so long for the promise of gene therapy either. Childers is hopeful that Audentes Therapeutics, a San Francisco biomedical company hes collaborating with (and which partially funded the current study), will begin their first human trials of a gene therapy treatment for x-linked myotubular myopathy, based on his teams research, later this year.

The teams findings were published earlier this February in Molecular Therapy.

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Gene Therapy Saves Puppies From A Fatal DiseaseAnd Maybe Us Next - Vocativ

By: PTI | Updated: February 20, 2017 6:53 pm Not only did mRNA technique make the mouse glow, it also later ran around, completely unaware of the complex series of events that had just taken place within its body, researchers said. ( Image for representation, Source: Youtube)

Stanford scientists have successfully developed glow-in-the-dark mice using compounds that create proteins responsible for lighting up fireflies, an advance that may pave the way for new gene therapies.

Timothy Blake, a postdoctoral fellow at Stanford University in the US refined compounds that carry instructions for assembling the protein that makes fireflies light up and delivered them into the cells of an anaesthetised mouse.

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Not only did the technique make the mouse glow, it also later woke up and ran around, completely unaware of the complex series of events that had just taken place within its body, researchers said.

This success could mark a significant step forward for gene therapy. It is hard enough getting these protein instructions, called messenger RNA (mRNA), physically into a cell. It is another hurdle altogether for the cell to actually use them to make a protein. If the technique works in people, it could provide a new way of inserting therapeutic proteins into diseased cells.

Its almost a childlike enthusiasm we have for this, said Robert Waymouth, a professor at Stanford. The code for an insect protein is put into an animal and that protein is not only synthesised in the cells but its folded and it becomes fully functional, capable of emitting light, said Waymouth. Although the results are impressive, this technique is remarkably simple and fast. Unlike traditional gene therapy that permanently alters the genetic makeup of the cell, mRNA is short-lived and its effects are temporary.

The transient nature of mRNA transmission opens up special opportunities, such as using these compounds for vaccination or cancer immunotherapy. Gene therapy is a decades-old field of research that usually focuses on modifying DNA, the fundamental genetic code. That modified DNA then produces a modified mRNA, which directs the creation of a modified protein.

Also Read:Gene-editing cell therapy saves two babies from cancer

The current work skips the DNA and instead just delivers the proteins instructions. They used a novel, deceptively straightforward creation, called charge-altering releasable transporters (CARTs). What distinguishes this polycation approach from the others, which often fail, is the others dont change from polycations to anything else, said Paul Wender, professor at Stanford.

Whereas, the ones that were working with will change from polycations to neutral small molecules. That mechanism is really unprecedented, Wender said. As part of their change from polycations to polyneutrals, CARTs biodegrade and are eventually excreted from the body.

One application of this technology is vaccination. At present, vaccines require introducing part of a virus or an inactive virus into the body in order to elicit an immune response. CARTs could potentially cut out the middleman, directly instructing the body to produce its own antigens.

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Stanford scientists create glow-in-the-dark mice, may advance gene therapies - The Indian Express

PMLiVE

Cell and gene therapies: on course for commercial success? PMLiVE Funding and reimbursement of cell and gene therapies pose a major challenge as payers consider how to evaluate a commercial proposition that is completely divergent from the traditional pharmaceutical model. Commenters, including the Regenerative ...

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Cell and gene therapies: on course for commercial success? - PMLiVE

FierceBiotech

Gene therapy treats muscle-wasting disease in dogs: Single infusion ... Science Daily Dogs with an inherited muscle-wasting disorder that was treated with a single infusion of corrective gene therapy were indistinguishable from normal animals ... Gene therapy tried in dogs with muscle disease could prove useful ...FierceBiotech all 2 news articles »

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Gene therapy treats muscle-wasting disease in dogs: Single infusion ... - Science Daily

Science Daily

Glowing mice suggest new gene therapy technique -- ScienceDaily Science Daily A collaboration between chemists and gene therapy experts produced a new way of inserting the code for modified proteins into the cells of mice. If successful in ... and more »

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Glowing mice suggest new gene therapy technique -- ScienceDaily - Science Daily

As the science behind genetic engineering and gene therapy has evolved in recent years scientists, ethicists and legislators have worked to set limits to the research. One critical line in the sand has been a consensus, endorsed by ethics councils and even a legally binding Council of Europe convention signed by 40 states (though not Ireland), that interference with, or editing, of human eggs, sperm or embryos to create genetic traits that can be inherited by future generations, so-called germ line engineering, has been strictly taboo.

The idea of human intervention in our own evolution rang alarm bells, conjuring up dystopian fears of scientists in their labs breeding a super-race or cosmetically engineering traits like strength, beauty and intelligence. The commercial opportunities are mind-boggling... but the technology simply did not allow it and so the line in the sand was largely academic.

Not so anymore. Recent advances, notably a powerful gene-editing tool called Crispr, have made snipping out tageted parts of the DNA of germline and non-germline, somatic, genes a relatively simple process. And the ethical debate has reopened. A report this week from two high level US scientific bodies US argues that germline editing should be allowed in very limited circumstances under strict supervision only alterations designed to prevent babies from acquiring genes known to cause serious diseases and disability, and only when there is no reasonable alternative.

If , for example, it were to become possible to edit the genes of someone with Huntingtons, a dreadful, incurable, inherited brain disease, so that the condition could not be passed on to successive generations, why not? How would that be qualitatively different ethically from the somatic gene therapy already widely practised?

In theory, that is. However there will be a particularly tough onus on researchers to show that the techniques when applied to the germline can be perfected to the point where such snipping does not involve off-target parts of the DNA or produce other consequences unrelated to this pupose in subsequent generations. We must hasten slowly.

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Emergence of Crispr provides opportunity to play God with gene therapy - Irish Times

CTVNews.ca Staff Published Friday, February 17, 2017 8:40AM EST Last Updated Friday, February 17, 2017 11:15AM EST

In what is being called a worlds first, a Canadian medical team has introduced a gene into a Calgary man with the hopes of combating a rare and life-threatening genetic disorder.

Preliminary results, doctors say, are promising, leading to a possible breakthrough in genetic disease treatment in humans.

According to a 2013 statement from Alberta Health Services, approximately 400 Canadians have Fabry disease. The inherited enzyme deficiency can shorten the lifespan of people who have it by as much as 40 years.

A team led by Dr. Aneal Khan, a medical geneticist at the University of Calgary and the Alberta Childrens Hospital, treated Darren Bidulka, a 48-year-old man who has a genetic disorder known as Fabry disease.

Patients with the genetic disease are unable to produce the enzyme that breaks down a fatty substance known as Gb3. When it builds up, it can severely damage the kidneys, heart and brain. Due to his condition, Bidulka undergoes two hours of enzyme-replacement therapy every two weeks.

Bildulkas gene therapy began when his medical team harvested his bone marrow. The stem cells were sent to the Toronto office of Dr. Jeffrey Medin, a specialist in gene transfer. His team took the cells and using a modified virus called a lentivirus, inserted a working copy of the malfunctioning gene into the stem cells.

The idea is that the corrected functional gene will cause the cells to produce the correct enzyme.

We injected the cells back into the patient, and the patients immune system has recovered, the patient is back on their regular enzyme-replacement therapy as well, Dr. Khan told CTV Calgary.

Aware of the risk involved with a new treatment method, Bidulka said he was initially cautious.

I looked at the risk, I looked at the rewards, and ultimately decided it was the right thing for me to do, said Bidulka. Initially there was some hesitancy to be the first in the world to do something.

The therapy isnt meant to cure Bidulkas condition; at this point, researchers want to know if its safe to perform on humans and if they are able to successfully insert the gene.

Preliminary results, Dr. Khan said, are promising.

We did some blood work to see if the copy of the gene we inserted made it to the patient and the bloodwork shows that it is in the blood of the patient, Dr. Khan said.

Researchers will monitor Bidulka for the next five years, with the hope that this is a new era for treatment in rare diseases.

Were working towards a cure, Dr. Khan said. I dont think were there yet.

Bidulka said he hopes that ultimately something is learned from the process that benefits people with Fabry Disease and other people with genetic disorders.

With files from CTV Calgary

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Calgary man becomes world's first to receive experimental gene therapy - CTV News

Hannahs Hope is a charity that was formed in 2008 after then-Plattsburgh residents Lori and Matt Sames daughter was diagnosed with a rare progressive nerve disease. Known informally as GAN, the disease appears in early childhood and slowly destroys the central nervous system. Hannah, who recently underwent gene therapy, and her mother Lori spoke about the disease and her progress.

GAN or Giant Axonal Neuropathy impacts sensory and motor neurons that govern movement and sensation. Nerve proteins fail to communicate between the peripheral and central nervous system. Patients generally die by their 20's or 30s.

Diagnosed at age 3, Hannah Sames will be 13 years old in March. She says she is doing pretty well. My legs feel the same. But my mom says Im strong. Lori Sames: She said her legs feel the same but my mom says they're stronger. She's gained twelve pounds. So and she can still be weight bearing and stand herself up so I call that a win.

Lori Sames explains that her daughter was the second of five children to undergo experimental gene therapy at the University of North Carolina Gene Therapy Center to combat the condition. She was injected on July 21 and in theory gene therapy is a one and done. So they deliver a healthy copy of the gene in a viral capsid. The virus attacks the nerve cells and infects it with a healthy copy of the gene. That in theory will have lifelong expression of the missing protein. So with Giant Axonal Neuropathy in this clinical trial Hannah and these children the first ever to receive a therapeutic gene to the spinal cord. So it's experimental. But it's not a continuously administered therapy. In theory it's a one and done.

Hannah reports that she was asleep during the actual treatment and since then has seen improvements in her mobility. My fiber motor is a lot better. Lori: She said her fiber motor is a lot better. She's able to grab cards better and flip them on demand. Last week we're at the National Institutes of Health where the clinical trial is taking place. Hannah was having her six month post injection followup assessments. And she would just grab a card, pick it up, flip it over effortlessly and very coordinated. And after the third card I looked at her and I said Hannah look at the control you have over your hand to flip those cards. In that moment she realized wow I didn't used to be able to do that.

Lori Sames explains that gene therapy targets specific cell types and this first effort for GAN targets nerves in the brain and spinal cord. GAN, Giant Axonal Neuropathy, is a disease of every cell type in the body. So while we hope that this stops the progression of the disease in the central nervous system we also are working on approaches to treat the nerves in the peripheral nervous system. And we're also following very closely gene delivery to the optic nerve program that's underway at U.N.C. that right now is funded by the National Institutes of Health through grants. We're also working on drug discovery. We hope to find small molecule or some compounds that may help also alleviate some of the pathology that we're seeing in the neurons in the peripheral nervous system.

Giant Axonal Neuropathy is rare and inherited through a single recessive gene. Most patients become quadriplegic as it becomes more severe. A common characteristic of most of those with the disease is very kinky curly hair.

Hannah's Hope: http://www.hannahshopefund.org/

NIH: U.S. National Library of Medicine: https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy

National Organization for Rare Disorders: https://rarediseases.org/rare-diseases/giant-axonal-neuropathy/

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Hannah's Hope Namesake And Mother Discuss Gene Therapy ... - WAMC

Arthrogen will start a Phase Ib trial for a gene therapy aiming to treat rheumatoid arthritis with a single injection and reduce costs for patients.

Arthrogen,based in Amsterdam, is developing local gene therapies for inflammatory diseases. The biotech company has now announced it has received approval to start a Phase Ib trial with its lead candidate, ART-I02, in patients with rheumatoid arthritis who still suffer from inflamed joints despitemultiple treatments.

The clinical trial will be conducted by the Centre for Human Drug Research (CHDR) in Leiden, with collaboration from other University Medical Centers in the Netherlands. Patients will start to be recruited in the first quarter of this year and results are expected by the end of 2018.

ART-I02 consists of a recombinant adeno-associatedviral vector (rAAV) genetically engineered to encode the human interferon (hIFN-) protein, which has anti-inflammatory activity.By including an inflammation-inducible promoter in the genetic construct, the gene is only expressed when the patient suffers flares of acute pain and inflammation.

Founded in 2005 as a joint venture between the Dubai Bone & Joint Center (DBAJ) in the United Arab Emirates and the Academic Medical Center (AMC) in Amsterdam, Arthrogen has managed to raise almost 15M so far to support its pipeline for inflammatory disease.

One of the advantages of ART-I02 is that its delivered locallyin the rheumatic joint, only affecting the target area to minimize side effects. In addition, gene therapy offers a long-lasting treatment with a single injection, which can significantly reduce costs for patients in the long term. However, Arthrogen will have to be careful to not follow the steps of its neighboruniQure, whose firstcommercial gene therapy was a failure because of pricing issues.

Rheumatoid arthritis is a big market, expected to generate 32.5B ($34.6B) by 2020. The space is crowded, but by then blockbusters like top-seller Humira will no longer be protected by patents in both the US and Europe, leading the way for biosimilars and other options affordable in the long term such as gene therapy.

Images byMidas Anim; Tefi /Shutterstock

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Gene Therapy for Rheumatoid Arthritis gets Approval to Start Clinical Trials - Labiotech.eu (blog)

Cancer is a nasty disease that affects millions of people throughout the world. With as many as one on every two people being diagnosed with some form of cancer during their lives, its imperative that effective treatments are found to try and help those in need. While researchers and scientists work around the clock trying to put an end to the disease, sadly, there is still no cure. However, one new trial involving gene therapy treatment may bring a new wave hope to cancer patients and has already proved to be successful.

This new form of treatment works by removing cancer-fighting cells from the tumor, multiplying them by billions in the lab, and then popping them back into the patients body ready to attack the disease. One patient who has benefited greatly from this treatment is 51-year old Celine Ryan. She has diagnosed with stage 4 colon cancer over three years ago, and despite radiation, chemotherapy, and surgery, cancer had spread to her lungs and was threatening her life considerably. It was partly due to Ryans abnormal genetic makeup that researchers could work out how to attack the mutation thats the cause of many cancers.

In March 2015 Ryan was accepted onto the gene therapy trial and after spending a month in the hospital, letting the treatment do its thing, six out of the seven tumors she had disappeared. The treatment does not work for everyone, but every time its tried is another opportunity to learn something new. Dr. Steven Rosenberg is a leading researcher in immunotherapy at the National Cancer Institute in Bethesda, Maryland and heads the gene therapy trail. He says, Many have not responded. But from every patient that we treat, whether their cancers go away or not; we learn something. But, the treatment worked for Ryan, and she is now celebrating ten months of being cancer free. Moving forward, Rosenberg explains, We can do, and are planning to do, that kind of gene therapy using the exact receptor we got from Celines cells to treat other people.

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Gene Therapy Treatment Offered to Cancer Patients Saves Lives - TrendinTech

uniQure plots to initiate a three-pronged clinical trial program next year as key assets from its in-house pipeline and Bristol-Myers Squibb collaboration advance. uniQure aims to move its hemophilia B gene therapy, AMT-060, into a pivotal trial while working to advance a Huntington's disease asset and Bristol-Myers-partnered heart failure candidate into the clinic.

Matthew Kapusta, who took over as CEO of uniQure in September, detailed the strategy in a talk(registration required)at Leerinks healthcare conference. The plan will follow the strategy uniQure set out in November when it laid off workers and stepped down its interest in Sanfilippo B and Parkinsons disease to prioritize investment in the aforementioned three programs.

The closely watched hemophilia B remains the centerpiece of the company. While investors weredisappointed by the Factor IX activity presented in a succession of readoutsespecially when compared to data from Spark Therapeutics rival gene therapyuniQure maintainedAMT-060 has a compelling efficacy and safety profile.

Kapusta claimed patients, physicians and the FDA share uniQures focus on reductions in FIX transfusions and rates of spontaneous bleeding rather than FIX activity.

In the interaction that we had with the FDA, it was very clear that they were looking at defined clinical benefits. And I think they were defining clinical benefit not in terms of Factor IX activity but in terms of impact on annualized bleeding rate, he said.

uniQure will have another chance to hear the FDAs views at its end of phase 2 meeting set to take place before the end of the quarter. The meeting will mark the start of a process intended to lead uniQure into a pivotal trial next year.

The start of phase 3 should contribute to a busy year in the clinic for uniQure. Following a year ofcollaboration with Bristol-Myers working on manufacturing matters, uniQure is now in the middle of animal studies that could set it up to file an INDand possibly start a trialnext year. uniQure isrunning a dose expression study of the heart failure gene therapy in healthy and diseased pigs.

In parallel, uniQure is working to get its Huntington's disease asset into the clinic. The candidate,the result of a five-year project, uses the AAV5 vector to deliver a microRNA intended to silence the Huntington gene. In mice, administration of the gene therapy into the striatum led to a 50% knockdown in the cortex.

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uniQure details three-pronged gene therapy trial program - FierceBiotech

Timothy Blake, a postdoctoral fellow in the Waymouth lab, was hard at work on a fantastical interdisciplinary experiment. He and his fellow researchers were refining compounds that would carry instructions for assembling the protein that makes fireflies light up and deliver them into the cells of an anesthetized mouse. If their technique worked, the mouse would glow in the dark.

Colin McKinlay and Jessica Vargas are co-lead authors of research that could mark a significant step forward for gene therapy by providing a new way of inserting therapeutic proteins into diseased cells. (Image credit: L.A. Cicero)

Not only did the mouse glow, but it also later woke up and ran around, completely unaware of the complex series of events that had just taken place within its body. Blake said it was the most exciting day of his life.

This success, the topic of a recent paper in Proceedings of the National Academy of Sciences, could mark a significant step forward for gene therapy. Its hard enough getting these protein instructions, called messenger RNA (mRNA), physically into a cell. Its another hurdle altogether for the cell to actually use them to make a protein. If the technique works in people, it could provide a new way of inserting therapeutic proteins into diseased cells.

Its almost a childlike enthusiasm we have for this, said chemistry Professor Robert Waymouth, co-senior author of the study. The code for an insect protein is put into an animal and that protein is not only synthesized in the cells but its folded and it becomes fully functional, capable of emitting light.

Although the results are impressive, this technique is remarkably simple and fast. And unlike traditional gene therapy that permanently alters the genetic makeup of the cell, mRNA is short-lived and its effects are temporary. The transient nature of mRNA transmission opens up special opportunities, such as using these compounds for vaccination or cancer immunotherapy.

Gene therapy is a decades-old field of research that usually focuses on modifying DNA, the fundamental genetic code. That modified DNA then produces a modified mRNA, which directs the creation of a modified protein. The current work skips the DNA and instead just delivers the proteins instructions.

Previous work has been successful at delivering a different form of RNA called short interfering RNA, or siRNA but sending mRNA through a cell membrane is a much bigger problem. While both siRNA and mRNA have many negative charges so-called polyanions mRNA is considerably more negatively charged, and therefore more difficult to sneak through the positively charged cell membrane.

What the researchers needed was a positively charged delivery method a polycation to complex, protect and shuttle the polyanions. However, this alone would only assure that the mRNA made it through the cell membrane. Once inside, the mRNA needed to detach from the transporter compound in order to make proteins.

The researchers addressed this twofold challenge with a novel, deceptively straightforward creation, which they call charge-altering releasable transporters (CARTs).

What distinguishes this polycation approach from the others, which often fail, is the others dont change from polycations to anything else, said chemistry Professor Paul Wender, co-senior author of the study. Whereas, the ones that were working with will change from polycations to neutral small molecules. That mechanism is really unprecedented.

As part of their change from polycations to polyneutrals, CARTs biodegrade and are eventually excreted from the body.

This research was made possible through coordination between the chemists and experts in imaging molecules in live animals, who rarely work together directly. With this partnership, the synthesis, characterization and testing of compounds could take as little as a week.

We are so fortunate to engage in this kind of collaborative project between chemistry and our clinical colleagues. It allowed us to see our compounds go from very basic building blocks all the way from chemicals we buy in a bottle to putting a firefly gene into a mouse, said Colin McKinlay, a graduate student in the Wender lab and co-lead author of the study.

Not only did this enhanced ability to test and re-test new molecules lead to the discovery of their charge-altering behavior, it allowed for quick optimization of their properties and applications. As different challenges arise in the future, the researchers believe they will be able to respond with the same rapid flexibility.

After showing that the CARTs could deliver a glowing jellyfish protein to cells in a lab dish, the group wanted to find out if they worked in living mice, which was made possible through the expertise of the Contag lab, run by Christopher Contag, professor of pediatrics and of microbiology and immunology and co-senior author of the study. Together, the multidisciplinary team showed that the CARTs could effectively deliver mRNA that produced glowing proteins in the thigh muscle or in the spleen and liver, depending on where the injection was made.

The researchers said CARTs could move the field of gene therapy forward dramatically in several directions.

Gene therapy has been held up as a silver bullet because the idea that you could pick any gene you want is so alluring, said Jessica Vargas, co-lead author of the study, who was a PhD student in the Wender lab during this research. With mRNA, there are more limitations because the protein expression is transient, but that opens up other applications where you wouldnt use other types of gene therapy.

One especially appropriate application of this technology is vaccination. At present, vaccines require introducing part of a virus or an inactive virus into the body in order to elicit an immune response. CARTs could potentially cut out the middleman, directly instructing the body to produce its own antigens. Once the CART dissolves, the immunity remains without any leftover foreign material present.

The team is also working on applying their technique to another genetic messenger that would produce permanent effects, making it a complementary option to the temporary mRNA therapies. With the progress already made using mRNA and the potential of their ongoing research, they and others could be closer than ever to making individualized therapeutics using a persons own cells. Creating a firefly protein in a mouse is amazing but, more than that, this research is part of a new era in medicine, said Wender.

Additional co-authors of this study, Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals, include Timothy Blake, Jonathan Hardy, Masamitsu Kanada and Christopher Contag. Waymouth is also a professor, by courtesy, of chemical engineering, a member of Stanford Bio-X, a faculty fellow of Stanford ChEM-H and an affiliate of the Stanford Woods Institute for the Environment. Wender is also a professor, by courtesy, of chemical and systems biology, a member of Stanford Bio-X, a member of the Stanford Cancer Institute and a faculty fellow of Stanford ChEM-H. Contag is also a professor, by courtesy, of radiology and of bioengineering, a member of Stanford Bio-X, a member of the Child Health Research Institute and a member of the Stanford Cancer Institute.

This work was funded by the Department of Energy, the National Science Foundation, the National Institutes of Health, the Chambers Family Foundation for Excellence in Pediatric Research, the Child Health Research Institute, the Stanford Center for Molecular Analysis and Design and the National Center for Research Resources.

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In a possible step forward for gene therapy, Stanford researchers made mice glow like fireflies - Stanford University News

Lonzas viral-based therapeutics unit Lonza Houston has agreed to manufacture an Anc80-AAVbased gene therapy product for Selecta Biosciences proprietary program for the treatment of methylmalonic acidemia (MMA) and may produce other Anc80-based products for which Selecta holds exclusive options, the companies said today.

The companies said their strategic manufacturing agreementwhose value was not disclosedwill apply to Selectas program Lonzas expertise in developing robust and industry-scale manufacturing platforms for viral-based products.

Lonza will utilize our extensive cGMP manufacturing knowledge and world-class quality systems to help Selecta Biosciences develop promising novel therapeutics for patients impacted by MMA and other devastating diseases, Andreas Weiler, Ph.D., head of the Emerging Technologies Business Unit for Lonzas Pharma & Biotech segment, said in a statement.

Anc80-AAV, an in silico-designed synthetic gene therapy vector, has generated preclinical data suggesting its potential to provide what the companies termed superior gene expression levels in the retina, liver, muscle, cochleas outer hair cells, and other tissue targets. Anc80-AAV has also shown reduced cross-reactivity compared to naturally occurring adeno-associated viral vectors (AAVs) now in clinical development, Lonza and Selecta said.

Selecta exclusively licensed Anc80 for MMA from Massachusetts Eye and Ear (MEE) in May 2016. The vector was developed by the laboratory of Luk H. Vandenberghe, Ph.D., director of MEEs Grousbeck Gene Therapy Center and an assistant professor at Harvard Medical School. Under the license agreement, whose value was not disclosed, Selecta also has the exclusive option to develop gene therapies using Anc80 for additional predefined lysosomal storage, genetic muscular, and genetic metabolic diseases.

Selecta focuses on combining novel and proprietary viral vectors with its immune tolerance Synthetic Vaccine Particles (SVP) to enable the first nonimmunogenic gene therapies, providing the potential for repeat dosing.

Selecta said it intends to combine Anc80 with recently discovered transgenes and Selectas SVP-Rapamycin to create a novel gene therapy candidate for MMA. The candidate will be designed to enable treatment of patients with and without pre-existing anti-AAV antibodies, prevent cellular immune responses that often reduce the expression levels of gene therapies, and provide the ability to administer repeat gene therapy doses to achieve sufficient levels of methylmalonyl-CoA mutase, the enzyme that MMA patients lack.

To advance the MMA program, Selecta last year entered into a Collaborative Research and Development Agreement (CRADA) with MEE and the NIHs National Human Genome Research Institute. The CRADAs principal investigators are Dr. Vandenberghe and Charles Venditti, M.D., Ph.D., senior investigator and head, Organic Acid Research Section, Medical Genomics and Metabolic Genetics Branch.

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Lonza to Manufacture Selecta Gene Therapy Candidate for MMA - Genetic Engineering & Biotechnology News

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease, according to scientists at the University of Washington (UW) Medicine Institute for Stem Cell and Regenerative Medicine.

The disease arises from a mutation in genes that normally make myotubularin, a protein essential for proper muscle function. Puppies with this naturally occurring mutation exhibit several features of babies with the same defective gene. The rare disorder, called X-linked myotubular myopathy, or XLMTM, affects only males. It causes fatal muscle wasting. Both dogs and boys with the disease typically succumb in early life due to breathing difficulties.

For decades, researchers have struggled to find suitable treatments for genetic muscle diseases like this one. Collaborating research groups in the United States and France found a way to safely replace the disease-causing MTM gene with a healthy gene throughout the entire musculature of affected dogs.

Their most recent findings ("Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs") werepublished online inMolecular Therapy.The paper reports that diseased dogs treated with a single infusion of the corrective therapy were indistinguishable from normal animals 1 year later.

"This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health," said Martin K. "Casey" Childers, Ph.D., UW medicine researcher and physician. Dr. Childers is a professor of rehabilitation medicine at the University of Washington School of Medicine and co-director of the Institute for Stem Cell and Regenerative Medicine.

Gene therapy holds the promise to treat many inherited diseases. To date, this approach has not been widely translated into treatment of skeletal muscle disorders.

"We report here a gene therapy dose-finding study in a large animal model of a severe muscle disease where a single treatment resulted in dramatic rescue," said Dr. Childers. The findings demonstrate potential application across a wide range of diseases and broadly translate to human studies. The data supports the development of gene therapy clinical trials for myotubular myopathy, the researchers concluded.

The study was conducted in collaboration with Harvard University, Medical College of Wisconsin, Virginia Tech, INSERM, and Genethon.

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Rare Muscle Disease Treated Successfully with Gene Therapy - Genetic Engineering & Biotechnology News

DUBLIN--(BUSINESS WIRE)--Research and Markets has announced the addition of Jain PharmaBiotech's new report "Gene Therapy - Technologies, Markets and Companies" to their offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2015, over 2050 clinical trials have been completed, are ongoing or have been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

Profiles of 188 companies involved in developing gene therapy are presented along with 233 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report.

Key Topics Covered:

Part I: Technologies & Markets

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety and Ethical Issues of Gene Therapy

11. Markets for Gene Therapy

12. References

Part II: Companies

13. Companies involved in Gene Therapy

For more information about this report visit http://www.researchandmarkets.com/research/npn4n6/gene_therapy

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Gene Therapy Technologies, Markets and Companies 2017 ... - Business Wire (press release)

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Lipid nanoparticles for gene therapy -- ScienceDaily - Science Daily

Human gene editing to prevent genetic diseases from being passed to future generations may be permissible under certain conditions, a panel of experts says.

Altering DNA in germline cells embryos, eggs, and sperm, or cells that give rise to them may be used to cure genetic diseases for future generations, provided it is done only to correct disease or disability, not to enhance peoples health or abilities, a report issued February 14 by the National Academies of Sciences and Medicine recommends. The decision contradicts earlier recommendations by organizers of a global summit on human gene editing, who concluded that gene editing with molecular scissors such as CRISPR/Cas9 should not be used to produce babies (SN: 12/26/15, p. 12).

Heritable gene editing is not yet ready to be done in people, says Alta Charo, a bioethicist at the University of WisconsinMadison Law School who cochaired the panel. We are not trying to greenlight heritable germline editing. Were trying to find that limited set of circumstances where its use is justified by a compelling need and its application is limited to that compelling need, says Charo. Were giving it a yellow light.

National Academies reports carry no legislative weight, but do often influence policy decisions in the United States and abroad. It will be up to Congress, regulatory agencies such as the U.S. Food and Drug Administration, and state and local governments to implement the recommendations.

Supporters of new genetic engineering technologies hailed the decision.

It looks like the possibility of eliminating some genetic diseases is now more than a theoretical option, says Sean Tipton, a spokesman for the American Society for Reproductive Medicine in Washington, D.C. Thats what this sets up. Diseases such as cystic fibrosis and Huntingtons, which are caused by mutations in single genes, could someday be corrected by gene editing. More complex diseases or disorders caused by changes in multiple genes, such as autism or schizophrenia, probably would not be the focus of genome editing.

Others worry that allowing any tinkering with the germline will inevitably lead to designer babies and other social ills. It raises fears of stigmatization of people with disabilities, exacerbation of inequalities between people who can afford such therapies and those who cant, and even a new kind of eugenics, critics say.

Once you approve any form of human germline modification you really open the door to all forms, says Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, Calif.

Panelist Jeffrey Kahn, a bioethicist at Johns Hopkins University, says the door to heritable gene therapy remains closed until stringent requirements can be met. Its frankly more of a knock on the door, he said at the public presentation of the report.

The report also changes the debate from whether to allow germline editing to instead focus on the line between therapy and enhancement, Darnovsky says. Im feeling very unsettled and disappointed by what they are recommending.

Several clinical trials in the United States, China and other countries are already under way to do gene editing in people who have cancer or other diseases. But those therapies do not involve altering germline cells; instead they fix defects or make alterations to DNA in other body, or somatic, cells. The panel recommended that such somatic cell therapies should also be restricted to treating diseases, not allowing enhancements.

Researchers in the United Kingdom, Sweden and China have already done gene editing on early human embryos in the lab. Recent clinical trials in Mexico and Ukraine to produce three-parent babies are also seen as altering the germline because such children carry a small amount of DNA from an egg donor (SN Online: 10/18/16). But those children dont have modifications of their nuclear DNA, where the genetic instructions that determine traits are stored.

Currently, researchers in the United States are effectively banned from conducting clinical trials that would produce heritable changes in the human genome, either by gene editing or making three-parent babies. The new recommendations could pave the way to allow such experiments.

But the panel lays out a number of hurdles that must be cleared before germline editing could move forward, ones that may be impossible to overcome, says Nita Farahany, a bioethicist at Duke Law School in Durham, N.C. Some people could read into the stringency of the requirements to think that the benefits could never outweigh the risks, she says.

One hurdle is a requirement to follow multiple generations of children who have gotten gene editing to determine whether the therapy has consequences for future generations. Researchers would never be able to guarantee that they could conduct such long-term studies, Farahany says. You cant bind your children and grandchildren to agree to be tracked by such studies.

Distinctions between therapies and enhancements are also vague. Researchers may not be able to convincingly draw lines between them, says George Church, a Harvard University geneticist who has developed CRISPR/Cas9 for a variety of purposes. Virtually everything medicine has accomplished could be considered as enhancing human life, he says. Vaccines are advancements over our ancestors. If you could tell our ancestors they could walk into a smallpox ward and not even worry about it, that would be a superpower.

But the new technology may make it harder to enhance humans than drugs do, says Charo. Gene-editing technologies are so precise and specific that someone who does not carry a disease-causing mutation would probably not benefit from the technology, she says.

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Human gene editing therapies are OK in certain cases, panel advises - Science News

An improved gene-therapy technique using a synthetic virushas restored the hearing of deaf mice up to the level of a whisper.

This technique might eventually be used to treat fetuses affected by Usher syndrome, a genetic condition responsible for three to six percent of childhood deafness, preventing them from being born deaf.

Last week, researchers at Harvard Medical School partially restored the hearing of genetically deaf mice using a separate gene therapy technique (see BioNews 887). Those mice were able to hear sounds at around 7080 decibels some mice in the present study could hear sounds as quiet as 2530 decibels.The treatment also restored the mice's balance, which is affected by the condition.

'Now, you can whisper, and they can hear you,' said Dr Gwenalle Gloc at Boston Children's Hospital, who led the study, which was published in Nature Biotechnology.

The mice were genetically engineered to have a mutation in the Ush1c gene, the same gene that causes Usher syndrome. The gene normally produces a protein called harmonin, without which the hair cells in the ear deteriorate.

Previous gene therapy techniques had only been able to penetrate the inner hair cells, but in a separate study in the same issue of Nature Biotechnology, scientists at Harvard demonstrated that they could penetrate 8090 percent of both inner and outer hair cells, using a synthetic virus to deliver a functional Ush1c gene into the cells.

Using this improved technique, Dr Gloc was able to treat the deaf mice. 'This strategy is the most effective one we've tested,' she said. 'Outer hair cells amplify sound, allowing inner hair cells to send a stronger signal to the brain. We now have a system that works well and rescues auditory and vestibular function to a level that's never been achieved before.'

After treatment the hair cells grew normally, and the effects persisted for at least six months. The mice had to be treated straight after birth or the therapy was not effective. The therapeutic window in humans would likely be in the uteruswhile the cochlea is still developing.

'This is a very encouraging result but it is only in a mouse model. One of the biggest risks is that the new synthetic viral vector has not been given to humans yet,' said Professor Alan Boyd, president of the Faculty of Pharmaceutical Medicine, who was not involved in the study. He estimates that human trials are at least three years away.

The researchers say that this approach could be effective for more than 100 genetic disorders that affect hearing in people.

Excerpt from:

Deaf mice able to hear 'whispers' after gene therapy - BioNews

Jesse Gelsinger (18 June 1981 17 September 1999) was the first person publicly identified as having died in a clinical trial for gene therapy. Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, the symptoms of which include an inability to metabolize ammonia a byproduct of protein breakdown. The disease is usually fatal at birth, but Gelsinger had not inherited the disease; in his case it was apparently the result of a spontaneous genetic mutation after conception and as such was not as severe some of his cells were normal, enabling him to survive on a restricted diet and special medications.

Gelsinger joined a clinical trial run by the University of Pennsylvania that aimed at developing a treatment for infants born with severe disease. On 13 September 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure. He died four days later at the age of 18, on 17 September at 2:30 pm, apparently having suffered a massive immune response triggered by the use of the viral vector used to transport the gene into his cells, leading to multiple organ failure and brain death.

A Food and Drug Administration (FDA) investigation concluded that the scientists involved in the trial, including the co-investigator Dr. James M. Wilson (Director of the Institute for Human Gene Therapy), broke several rules of conduct:

The University of Pennsylvania later issued a rebuttal,[1] but paid the parents an undisclosed amount in settlement. Both Wilson and the University are reported to have had financial stakes in the research.[2][3] The Gelsinger case was a severe setback for scientists working in the field.[4]

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Jesse Gelsinger - Wikipedia

MedicalResearch.com Interview with:

Dr. Gwenaelle Geleoc

Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Childrens Hospital and Harvard Medical School Boston, MA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.

MedicalResearch.com: What should readers take away from your report? Response: This work demonstrates that gene therapy treatments can efficiently restore auditory and balance function. The level of recovery that we have obtained has never been seen before. Having identified a potent vehicle and applying the treatment at the right time was crucial in our study.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We need to extend this work to other deafness genes that lead to congenital or progressive deafness. The difficulty will arise when looking at genes that extend beyond the capacity of the vector we used for this study. Any gene over 5kb will not fit in our vector. Other strategies will therefore be required.

MedicalResearch.com: Is there anything else you would like to add? Response: Our goal is to advance research to develop new treatments for deafness and balance disorders. I welcome collaborations and material sharing with anyone who wish to work with us for this purpose.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Gwenalle S Gloc et al. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nature Biotechnology, February 2017 DOI: 10.1038/nbt.3801

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Gene Therapy Restores Hearing Down To A Whisper, in Mice - MedicalResearch.com (blog)