Guangping Gao, PhD, is an internationally recognized gene therapy researcher who has played a key role in the discovery and characterization of new family of adeno-associated virus (AAV) serotypes, which was instrumental in reviving the gene therapy field, hugely impacting many currently untreatable human diseases. Dr. Gao is the Co-Director, Li Weibo Institute for Rare Diseases Research, Director, Horae Gene Therapy Center and Viral Vector Core, Professor of Microbiology and Physiological Systems, Penelope Booth Rockwell Professor in Biomedical Research, University of Massachusetts Medical School. For nearly 30 years of his scientific research career, Dr. Gao has primarily focused on molecular genetics and viral vector gene therapy of human diseases. He has published >230 research papers, 6 book chapters, and 4 edited books and serves as Editor of Human Gene Therapy, Senior Editor of the Gene and Cell Therapy book series, Associate Editor of Signal Transduction and Targeted Therapy, and on Editorial Boards of several other gene therapy and virology journals. He was recently elected for a three-year term as the Vice President (2017-2018), President elect (2018-2019) and President (2019-2020) for the American Society of Gene and Cell Therapy. Dr. Gao is an elected fellow of the US National Academy of Inventors (NAI), holding 131 patents with 221 more patent applications pending.

Watch this video for an introduction to gene therapy…

The following has been paraphrased from an interview with Prof. Gao Guangping on June 1st, 2018.

(Click above for the full audio version or here for a downloadable link)

Could you explain how adeno-associated viruses (AAVs, the virus most commonly used in gene therapy) are transforming our ability to tackle disease?

The first challenge in gene therapy is getting the transgene (an external therapeutic gene delivered into another organism) into enough cells, at high enough levels to be effective without toxicity. AAVs do this better than other viral vectors (tools used to deliver genetic material into cells) or other chemical delivery mechanisms, they are also not toxic to humans, and they can last for many years. AAVs will change the paradigm of disease treatment by allowing us to safely and effectively deliver genes that can help people fight disease.

What is your opinion of non-invasive gene therapy approaches designed to be delivered peripherally?

For diseases that affect only small regions of the brain, like Parkinson’s disease, you do not need systemic delivery of viruses. For other diseases, where the entire brain is affected, these kinds of broadly distributed gene therapy by systemic injections might work. But you also have to think about the cost of the drug, as you likely need a hundred times the amount to get the same efficiency as the local gene-delivery methods. Also, if you do a local injection, the chance of inducing an immune response is greatly reduced.

Why have previous gene therapies for Parkinson’s disease struggled?

There are multiple reasons, including delivery methods, dosage, and coverage. Gene therapy is much more complicated than conventional drug development, it is a systematic engineering process. This process has greatly improved over the years in terms of drug design, manufacturing, method of delivery, and understanding appropriate dosage. At the time of previous attempts we did not have a good enough understanding of the system needed to effectively deliver gene therapy.

One of the worries about the Voyager Therapeutics (which Dr. Gao co-founded) approach is that they are delivering viruses that cause neurons in the putamen (the part of the brain lacking dopamine in PD) to produce dopamine from L-dopa. However those cells don’t naturally have the machinery to package, release, and re-absorb dopamine in a controlled fashion. So, could this approach be detrimental to the neurons in the putamen?

That is a hypothesis. Collectively researchers have been studying this approach for almost 10 years, and so far we haven’t seen any issues related to toxicity. Voyageur has dosed 10 or so patients so far and we have seen functional benefit after gene therapy. Though these neurons may not be naturally designed to convert L-dopa into dopamine, the data indicates that it is working. Also, now when we deliver the viruses into the putamen we use MRIs to not only check the location but also the functional expression of the enzyme to make sure dopamine is being produced. We are still watching for long term effect of this treatment, but the data so far shows that it is working well.

Are public concerns about gene therapy being used to augment human abilities a legitimate concern?

Overall, it is a legitimate concern, particularly in places that lack regulation. But in America, gene therapy is highly regulated. Though there are people that sell do it yourself kits for gene therapy, we strongly discourage those kinds of practices. Years ago we published a paper on a gene therapy in monkeys that improved their durability and got them to produce more red blood cells. There were people that feared it might be used for gene doping in athletes, but soon afterwards researchers figured out ways to detect these transgenes and now athletic bodies can test for this kind of gene doping.

But, we in the gene therapy community are not interested in human enhancement, we only focus on disease treatment. There are crazy people doing crazy things, and from a scientific point of view it is possible to use these methods for human enhancement, however, I think it is unlikely because the global scientific community is well connected and strongly against such kind of malpractice, it would be hard for any group to pursue these things in isolation.

Click here to learn more about the gene therapy techniques being developed for Parkinson’s disease by Voyageur Therapeutics.