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Research on astrocyte\u2010centered diseases requires efficient and well\u2010characterized gene transfer vectors. Vectors derived from the Adeno\u2010associated virus serotype 9 (AAV9) target astrocytes in the brains of rodents and nonhuman primates. A recombinant (r) synthetic peptide\u2010displaying AAV9 variant, rAAV9P1, that efficiently and selectively transduces cultured human astrocytes, has been described previously. Here, it is shown that rAAV9P1 retains astrocyte\u2010targeting properties upon intravenous injection in mice. Detailed analysis of putative receptors on human astrocytes shows that rAAV9P1 utilizes integrin subunits <jats:italic>\u03b1<\/jats:italic>v, <jats:italic>\u03b2<\/jats:italic>8, and either <jats:italic>\u03b2<\/jats:italic>3 or <jats:italic>\u03b2<\/jats:italic>5 as well as the AAV receptor AAVR. This receptor pattern is distinct from that of vectors derived from wildtype AAV2 or AAV9. Furthermore, a CRISPR\/Cas9 genome\u2010wide knockout screening revealed the involvement of several astrocyte\u2010associated intracellular signaling pathways in the transduction of human astrocytes by rAAV9P1. This study delineates the unique receptor and intracellular pathway signatures utilized by rAAV9P1 for targeting human astrocytes. 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