Next Generation Gene Therapy - A Cell Specific Endeavour

Recent technological and conceptual advances have resulted in a plethora of exciting novel engineered adenoassociated viral (AAV) vector variants. Many of them with unique characteristics and abilities. However, so farthere are no cell specific AAVs and only one synthetic AAV has made it into the clinic.

Clinical trials have shownover the last decade that AAV is a safe and suitable vector for gene therapy but that it also is a vehicle that canbenefit significantly from improvement in specificity and potency.

A promising alternative to achieve cellspecificity is to incorporate short enhancer sequences upstream of minimal promoters.

In this project proposal Ipropose DNA barcoding to facillitate for massively parallel screenings of both avenues, using very few animals.By using DNA barcoding we can perform parallel screenings of both viral capsids and enhancer-promoters in thesame animals and we are confident we can reduce the number of animals by 99.999% compared to standardtechniques.

At the end of this four-year project, I will have:1) Generated and validated novel AAV capsids with selective infectivity.2) Identified enhancer-promoters for cell specific gene expression.3) Characterized AAV capsids and enhancer-promoters across species and ages.The completion of these studies will provide tremendous value to the scientific community, not only for the basicsciences, but also for future translational and therapeutic studies regarding gene therapy.