Genetically Engineered AAV Rep for Gene Targeting and rAAV Production

Background

Gene therapy strategies have exploited lenti or retro viral approaches for long-term gene replacement, however, their clinical applications remain limited because of potential for viral-associated oncogenesis. Recently, gene therapy strategies have attempted to use hybrid Adenovirus/Adeno-associated viruses (Ad/AAV) to combine the capacity, tropism and ease of production of adenovirus (Ad) with adeno-associated virus (AAVs) ability for site-specific integration (SSI). Although the AAV Rep78 protein is required for SSI, it also has an inhibitory effect on Ad replication, particularly when co-expressed within the Ad backbone leading difficulty in generating and integrating transgene within the back-bone of a single hybrid virus.

Technology

Researchers at Stony Brook University have identified a genetic element within the Rep gene sequence, which is inhibitory to Ad replication. This AAV Rep gene was then genetically recoded using synonymous codon pair re-engineering to overcome Reps inhibitory effects on Ad replication. The novel construct thus created provides a unique opportunity to place all genetic elements in one virus for the purpose of safely integrating a transgene into a specific region of the human genome.

Advantages

Combines the advantages of Ad (high titer, high infectivity and large capacity) and integration capability of AAV Offers one-step packaging systems for rAAV viral production.

Application

New Gene therapy vectors Improved rAAV production methods.

Patent Status

Patent application submitted

Stage Of Development

Pending US Utility covering compositions and methods of use

Licensing Potential

Licensing,Commercial partner,Development partner,Seeking investment

Licensing Status

Available for License. Stony Brook University seek to develop and commercialize, by an exclusive or non-exclusive license agreement and/or sponsored research, with a company active in the area.

Additional Info

https://stonybrook.technologypublisher.com/files/sites/tuspkx8qt1q4gszxjpze_r-8286-a-novel-hybrid-virus-for-gene-therapy-for-long-term-expression-of-large-dna-segments-header.jpeg Please note, header image is purely illustrative. Source: rost9, stock.adobe.