Abstract: Precise targeting of specific regions within the central nervous system (CNS) is crucial for both scientific research and gene therapy in the context of brain diseases. Adeno-associated virus 13 (AAV13) is known for its restricted diffusion range within the CNS, making it an ideal choice for precise labeling and administration within small brain regions. However, AAV13 mediates relatively low expression of target genes. Here, we introduced specific engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency. Firstly, we constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid. Furthermore, we inserted the 7m8 peptide, known to enhance cell transduction, into positions 587/588 and 585/586 of the AAV13 capsid, resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8, respectively. We found that AAV13-YF exhibits superior in vitro infectivity in HEK293T cells compared to AAV13, while AAV13-587-7m8 and AAV13-585-7m8 display enhanced CNS infection capabilities in C57BL/6 mice. These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.