Jason Fontenot, PhD, on Overcoming the Challenge of Delivery for Zinc Finger Epigenetic Repressors

“Our vision is that we can use our [ZF] platform to repress the tau protein, which is implicated in Alzheimer disease progression in a once-and-done way to essentially stop the progression of Alzheimer disease. It has huge potential for a huge population of people.”

Although investigational genomic medicines have shown great potential for treating a wide range of diseases, delivering these therapies to target tissues remains a challenge, especially in neurological indications such as Alzheimer disease. As such, the identification of new delivery tools, such as novel adeno-associated virus capsids, is of particular interest.

Sangamo Therapeutics presented several posters covering its research into AAV capsid evolution at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California. A goal of the work is to identify capsids suitable for widespread delivery of genomic medicines throughout the brain, as this distribution is likely necessary to effectively treat conditions such as Alzheimer disease and Parkinson disease.

In an interview with CGTLive™, Jason Fontenot, PhD, the chief scientific officer of Sangamo Therapeutics, discussed the company’s methods for capsid evolution and how the work goes hand in hand with the company’s research into zinc finger (ZF) genome regulation, which could provide the possibility of treating conditions such as these by regulating the expression of relevant genes. He noted that although the company’s initial 2 programs for ZF epigenetic repression focus on conditions which are more straightforward to target with currently available AAV delivery methods, namely NaV1.7-associated small fiber neuralgia and Creutzfeldt-Jakob disease, the targeting of Alzheimer disease is an important longer-term goal for the company. He also briefly touched on the importance of in vivo studies as a milestone in the development of its 2 preclinical ZF genome regulation programs and expressed optimism about future synergy between the company’s ZF platform and the capsid evolution research.

REFERENCE
1. Sangamo Therapeutics to present pre-clinical data from its genomic engineering platform at the 26th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT). News release. Sangamo Therapeutics, Inc. May 2, 2023. Accessed May 18, 2023. https://investor.sangamo.com/news-releases/news-release-details/sangamo-therapeutics-present-pre-clinical-data-its-genomic