In vivo selection of adeno-associated virus (AAV) variants targeting special tissues. The AAV library with diversified cap genes was injected into adult C57BL/6J mice via the tail vein. Genomic DNA was isolated from the target organs, i.e., the heart or skeletal muscle, and used for PCR amplification of AAV cap genes. The selected cap gene mutants were re-cloned into plasmid vector with AAV rep gene and ITR sequences. The generated plasmid libraries were used for sequence analysis of cap genes and production of AAV libraries for the next screening cycle in mice. After a few rounds of in vivo biopanning, the cap genes enriched in the heart or skeletal muscle but relatively rare in the liver were used for packaging of recombinant AAV vectors for characterization of their tissue tropism.