Persistent Gene Transfer to Mitochondria
Abstract
The major goal of this project was to achieve persistence of gene expression after delivery of an exogenous genome to mitochondria. The project was based on published observations that insertion of a mitochondrial targeting peptide sequence into the capsid of an AAV serotype 2 vector would permit delivery of the AAV2 vector genome to mitochondria. The AAV vector included a gene expression cassette that contained a mitochondrial promoter, terminator, and an open reading frame consistent with the mitochondrial transcription and translation. An AAV2 vector was synthesized, but gene expression was not observed in mitochondria and the vector yield was low. The system was reconstructed using AAV8 as the base serotype. The vector was synthesized, but the project ended before the new system could be tested. As a result, the specific aims of the project that focused on the fate of adeno-associated viral vector backbones were not tested. In addition, while the vector constructs included mitochondrial tRNAs as part of their design, the goal of expressing exogenous mitochondrial tRNAs in models of mitochondrial diseases such as MERRF and MELAS remains to be tested.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1104268
Entities
People
- Philip L. Leopold
Organizations
- Weill Cornell Medicine