Vice president of neuroscience at Sangamo Therapeutics

Amy Pooler, PhD

“There are some advantages based on the fact that you could use a lower dose... it may also be able to evade some of the new neutralizing antibodies that we know are circulating in the in the bloodstream and target directly the CNS rather than increasing exposure in some of the peripheral organs.”

While gene and cell therapies have the potential to treat many rare, neurological diseases, efficient gene delivery to the central nervous system (CNS) remains a barrier to developing these therapies. One possible avenue of gene delivery lies in the cerebrospinal fluid; however, more work is needed to make this approach feasible for CNS disorders.

Sangamo Therapeutics’ new platform, SIFTER (Selecting In vivo for Transduction and Expression of RNA), is designed to engineer capsids with improved neuronal transduction after CSF administration. Preclinical data on this platform was presented at 

American Society of Gene & Cell Therapy 25th Annual Meeting

 (ASGCT), held in Washington, DC, and virtually May 16-19, 2022, by David S. Ojala, PhD, senior scientist, AAV engineering, Sangamo Therapeutics.

spoke with Amy Pooler, PhD, vice president of neuroscience, Sangamo Therapeutics, to learn more about the platform and how it combats challenges with gene delivery to the CNS. She discussed novel capsids identified with SIFTER that showed improved neuronal transduction.

Ojala DS, Andrews L, Nanjaraj A, et al. Engineered AAV capsids exhibit improved transduction of the central nervous system after CSF administration in adult cynomolgus macaques. Presented at: ASGCT 25th Annual Meeting, May 16-19, 2022, Washington DC. Abstract #441.

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The vice president of neuroscience at Sangamo Therapeutics discussed identifying novel capsids with improved neuronal transduction to the CNS. 

Amy Pooler, PhD, on Improving Gene Delivery to the CNS 

“The whole field of genomic medicine is really starting to open up. I think this is thanks to both the improved science and understanding of disease biology and also the availability of these new genomic medicine techniques. It's a really exciting time for neuroscience, because we may be able to finally intervene in some of these debilitating diseases in a way that could potentially deliver curative therapies.”

Sangamo Therapeutics is working to develop several new gene editing techniques, including their zinc finger protein (ZFP) technology in use in multiple central nervous system (CNS) disorders. Data from preclinical studies using ZFPs were presented at the 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), May 12-15, 2021.

Sangamo cites the single-nucleotide precision, high efficiency, and high-specificity that ZFPs are designed to achieve that will limit off-target effects while effectively targeting genome sequences.

 Preclinical research has shown the the potential of AAV-ZFP-transcription factors as a therapeutic approach in Parkinson disease, with evidence of downregulated alpha-synuclein mRNA expression in the brain.

spoke with Amy Pooler, PhD, vice president of neuroscience at Sangamo Therapeutics, to learn more about the neuroscience research landscape and advances that are being made with gene editing and disease biology. She discussed several avenues the company is exploring with the ZFP platform and partnerships to advance research the company is involved in.

1. Hatami A, Nguyen H, Roth T, et al. Alpha-synuclein repression using zinc finger protein transcription factors - A novel therapeutic approach for the treatment of Parkinson’s disease. Presented at: 2021 American Society of Gene & Cell Therapy Annual Meeting; May 12-15, 2021. Abstract 539.
2. Zinc Finger Platform. Sangamo Therapeutics. 2021. 

https://www.sangamo.com/technology/zinc-finger-platform

The head of neuroscience at Sangamo Therapeutics discussed advances in understanding disease biology that allow for more specific gene targeting. 

Targeting CNS Disorders With Precision Gene Editing

“The zinc fingers are using specifically designed versions of what our cells are already doing to regulate gene expression in the brain. We pair these ZFPs with the functional protein in order to create ZFP transcription factors. This functional domain could be anything; it could be something to upregulate or downregulate gene expression. We’re using this approach to target a wide array of neurological diseases.”

Among recent gene editing innovations is Sangamo Therapeutics’s zinc finger protein technology (ZFP), several abstracts on which were presented at the 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), May 12-15, 2021.

ZFPs are designed to be able to target genome sequences with single-nucleotide precision, high efficiency, and high specificity to limit off-target effects.

 Preclinical research presented at ASGCT showed the potential of AAV-ZFP-transcription factors as a therapeutic approach in Parkinson disease, with evidence of downregulated alpha-synuclein mRNA expression in the brain.

 spoke with Amy Pooler, PhD, vice president of neuroscience at Sangamo Therapeutics, to learn more about the potential of ZFPs in treating a variety of central nervous system disorders. She also discussed the advantages of the technology over other gene editing strategies.

1. Hatami A, Nguyen H, Roth T, et al. Alpha-synuclein repression using zinc finger protein transcription factors - A novel therapeutic approach for the treatment of Parkinson’s disease. Presented at: 2021 American Society of Gene & Cell Therapy Annual Meeting; May 12-15, 2021. Abstract 539.
2. Zinc Finger Platform. Sangamo Therapeutics. 2021. https://www.sangamo.com/technology/zinc-finger-platform

The head of neuroscience at Sangamo Therapeutics discussed the potential of ZFPs in central nervous system disorders. 

Amy Pooler, PhD

Articles

Amy Pooler, PhD, on Improving Gene Delivery to the CNS

Targeting CNS Disorders With Precision Gene Editing

Precision Gene Editing With Zinc Finger Protein Technology