Why the study?
Does a massively parallel in vivo evaluation pipeline identify AAV variants with superior muscle tropism in adult mice?
Does a massively parallel in vivo evaluation pipeline identify AAV variants with superior muscle tropism in adult mice?
A novel high-throughput in vivo screening pipeline identified AAVMYO, an AAV9 variant with superior tropism for skeletal and cardiac muscle, holding potential for muscle gene therapy.
AAVMYO may advance muscle gene therapy vectors in mice; leaves open translation to human cardiac and skeletal muscle disorders.
Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, we create three independent libraries comprising 183 different AAV variants including widely used benchmarks and screened them in all major tissues in adult mice. Thereby, we discover a peptide-displaying AAV9 mutant called AAVMYO that exhibits superior efficiency and specificity in the musculature including skeletal muscle, heart and diaphragm following peripheral delivery, and that holds great potential for muscle gene therapy. Our comprehensive methodology is compatible with any capsids, targets and species, and will thus facilitate and accelerate the stratification of optimal AAV vectors for human gene therapy.
No takes yet. Share an insight, caveat, or question.
Weinmann et al. (2020) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: