Protein Replacement Therapy Using Gene Delivery
Dr. Kevin Nash, a researcher at the University of Florida, is working on protein replacement therapy using gene delivery. He is using adeno-associated virus (AAV) as a tool for gene therapy, particularly for neurological diseases such as Alzheimer’s and Parkinson’s disease. AAV is a non-pathogenic virus that can infect both dividing and non-dividing cells, making it suitable for targeting neurons. It has the advantage of long-term expression and does not integrate into the genome, reducing the risk of causing cancer. Dr. Nash is also exploring alternative methods to achieve more widespread distribution of the virus in the brain, such as using the ventricular system or targeting interconnecting pathways.
In this talk, Dr. Kevin Nash discusses his work on protein replacement therapy using gene delivery. Dr. Nash is a member of the FIRE team at the University of Florida and has been invited to join the team thanks to the support of the FAST team and their fundraising efforts.
Dr. Nash provides some background information on his research journey. He graduated from the University of Queensland and then moved on to the University of Florida, where he worked on adeno-associated virus (AAV) and became interested in its potential as a tool for gene therapy. He started collaborating with researchers at the University of South Florida, focusing on neurological diseases such as Alzheimer’s and Parkinson’s disease. Dr. Nash also began collaborating with Dr. Weeber on Angelman syndrome.
Advantages of AAV
Dr. Nash highlights the advantages of using AAV as a viral vector for gene therapy. AAV is non-pathogenic, meaning it does not cause disease in humans. It does not elicit a strong immune response and can infect both dividing and non-dividing cells, making it suitable for targeting neurons. AAV remains episomal, meaning it does not integrate into the genome and reduces the risk of causing cancer. AAV also allows for long-term expression of the gene of interest and does not contain viral genes that could trigger an immune response.
AAV as a Tool for Gene Delivery
Dr. Nash explains the structure of AAV and how it can be modified for gene delivery. AAV is a simple virus with a small genome and only two proteins. These proteins can be removed and replaced with the gene of interest. The promoter, which drives the expression of the gene, can also be changed to target specific cells or regions. Dr. Nash provides an example of injecting AAV into the hippocampus of a mouse and achieving targeted gene expression.
Expanding Distribution in the Brain
One limitation of AAV is its limited distribution to the site of injection. Dr. Nash discusses his interest in finding alternative methods to achieve more global distribution of the protein therapy in the brain. He explores the use of the ventricular system, which produces spinal fluid within the brain, as a means to distribute the protein throughout the brain. By injecting AAV into the ventricles, the cells lining the system can act as small factories to produce and deliver the protein to the rest of the brain. Dr. Nash also mentions the use of intrathecal injection, where AAV can pass out of the spinal fluid and infect cells within the brain, allowing for broader distribution.
Targeting Interconnecting Pathways
Dr. Nash’s research also focuses on targeting interconnecting pathways within the brain. He explains that different regions of the brain are interconnected and wants to explore if he can use these pathways to deliver the protein from one region to another. By infecting cells in one region, the protein can be delivered to other regions through these interconnecting pathways, potentially restoring normal function.
Dr. Nash concludes his presentation by thanking his colleagues and team members for their contributions to the project. His research on protein replacement therapy using gene delivery shows promise in treating neurological diseases and expanding the reach of the therapy within the brain.
- Title: Protein replacement therapy using gene delivery
- Author(s): Kevin Nash
- Author(s)’ affiliation: University of South Florida
- Publication date: 2015-12-04
- Collection: 2015 FAST Science Summit