Adeno-associated viral (AAV) vectors are highly efficacious gene therapy vectors are safe and highly efficacious for gene therapy and have advanced to clinical trials for a number of disorders. However, AAV vectors have a limited cargo capacity (4.7 kilobase pairs), thus over 20% of human genes are too large to be compatible with the vectors. Here, the inventors propose the use of compact ubiquitous mini-promoters that allow for increased space for packaging large genes in the vector while maintaining the high level of efficacy achieved with use of the standard promoters.

The mini-promoters are novel chimeric promotors consisting of 399 base pairs, compared to the 1.7 kilobase pair or 850 base pair promoters currently used. Despite their truncated size and in contrast to existing short promoters , these novel mini-promoters retain robust constitutive activity in preliminary in vitro studies. This technology will vastly expand the number of disorders treated by AAV vector-based gene therapy by enabling incorporation of genes that were previously incompatible with AAV vectors.

The inventors have completed in vitro studies using multiple cell lines. They are continuing their studies with characterization of the mini-promoters in human brain organoids and in vivo studies in mouse models.