GSE145172 In vivo high-throughput screening of novel adeno-associated viral capsids identifies variants for transduction of adult neural stem cells within the subventricular zone

Contributors : Sascha Dehler ; Lukas P Kremer ; Thomas Stiehl ; Jonas Weinmann ; Heike Abendroth ; Alexander Laure ; Anna Marciniak-Czochra ; Dirk Grimm ; Ana Martin-VillalbaSeries Type : OtherOrganism : Mus musculusThe adult mammalian brain entails a reservoir of neural stem cells (NSCs) generating glial cells and neurons. However, NSCs become increasingly quiescent with age, which hampers their regenerative capacity. New means are therefore required to genetically modify adult NSCs for re-enabling endogenous brain repair. Recombinant adeno-associated viruses (AAVs) are ideal gene therapy vectors due to an excellent safety profile and high transduction efficiency. We thus conducted a high-throughput screening of 157 intraventricularly injected barcoded AAV variants profiled by transcriptome sequencing. Transcriptome analysis identified two synthetic capsids, AAV9_A2 and AAV1_P5 transducing active and quiescent NSCs. Further optimization of AAV1_P5 by judicious selection of promoter and dose of injected viral genomes enabled targeting of 57% of the NSC compartment. Importantly, transduced NSC readily produced neurons. The present study identifies AAV variants with a high specificity and transduction efficiency of adult NSCs thereby paving the way for preclinical testing of regenerative gene therapy.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Mus musculus Source Type: research