The present disclosure provides recombinant adeno-associated virus (rAAV) virions comprising a variant AAV capsid protein, e.g., an AAV capsid protein derived from an ancestral AAV capsid protein amino acid sequence. An rAAV virion of the present disclosure can exhibit greater infectivity of a target cell. The present disclosure also provides methods of delivering a gene product to a target cell in an individual by administering to the individual an rAAV of the present disclosure. The present disclosure also provides methods of generating rAAV virions that have a variant AAV capsid protein derived from an ancestral AAV capsid protein amino acid sequence.