An adenovirus-associated virus capsid protein modified by deletion and/or substitution of one or more amino acid residues within the variable region 1 loop, wherein the capsid protein is serotype AAV1 having a VR1 loop of SEQ ID NO: 1, is serotype AAV6 having a VR1 loop of SEQ ID NO: 6, is serotype AAV8 having a VR1 loop of SEQ ID NO: 7, or is serotype AAV9 having a VR1 loop of SEQ ID NO: 8, to cause regional destabilization within the loop due to the targeted destruction of hydrogen bonding patterns orchestrated by the residues, wherein the capsid protein comprising the modification provides to a virus vector comprising the capsid protein increased transduction efficiency and/or modified tissue specificity relative to a virus vector comprising a capsid protein that does not contain the modification, wherein: a) the capsid protein is serotype AAV1 and has a deletion at position S1, S2, A3, S4, T5, G6, A7, S8, or N9 of SEQ ID NO: 1, wherein the capsid protein provides increased transduction efficiency of muscle relative to a virus vector comprising a capsid protein that does not contain the deletion; b) the capsid protein is serotype AAV6 and threonine at position 5 of SEQ ID NO: 6 is deleted, or serotype AAV8 and threonine at position 3 of SEQ ID NO: 7 is deleted, wherein the capsid protein provides increased transduction efficiency of muscle relative to a virus vector comprising a capsid protein that does not contain the deletion; c) the capsid protein is serotype AAV1 and has an amino acid substitution of T5E, T5F, or T5D in SEQ ID NO: 1, wherein the capsid protein provides to an AAV vector comprising the capsid protein increased muscle transduction efficiency by at least about 10% relative to a virus vector comprising a capsid protein that does not contain the modification; d) the capsid protein is serotype AAV9, and comprises an amino acid substitution of S3A and deletion of S5 of SEQ ID NO: 8, wherein capsid protein provides to an AAV vector comprising the capsid protein decreased hepatic transduction efficiency by at least about 10% relative to a virus vector comprising a capsid protein that does not contain the deletion or substitution; or e) the capsid protein is serotype AAV1 and comprises a substitution of aspartic acid at position 5 of SEQ ID NO: 1, or is serotype AAV6, and comprises a substitution of aspartic acid at position 5 of SEQ ID NO: 6, wherein the capsid protein provides to an AAV vector comprising the capsid protein increased muscle transduction efficiency by at least about 10%, and further provides increased hepatic transduction efficiency, relative to a virus vector comprising a capsid protein that does not contain the substitution. a) the capsid protein is serotype AAV1 and has a deletion at position S1, S2, A3, S4, T5, G6, A7, S8, or N9 of SEQ ID NO: 1, wherein the capsid protein provides increased transduction efficiency of muscle relative to a virus vector comprising a capsid protein that does not contain the deletion; b) the capsid protein is serotype AAV6 and threonine at position 5 of SEQ ID NO: 6 is deleted, or serotype AAV8 and threonine at position 3 of SEQ ID NO: 7 is deleted, wherein the capsid protein provides increased transduction efficiency of muscle relative to a virus vector comprising a capsid protein that does not contain the deletion; c) the capsid protein is serotype AAV1 and has an amino acid substitution of T5E, T5F, or T5D in SEQ ID NO: 1, wherein the capsid protein provides to an AAV vector comprising the capsid protein increased muscle transduction efficiency by at least about 10% relative to a virus vector comprising a capsid protein that does not contain the modification; d) the capsid protein is serotype AAV9, and comprises an amino acid substitution of S3A and deletion of S5 of SEQ ID NO: 8, wherein capsid protein provides to an AAV vector comprising the capsid protein decreased hepatic transduction efficiency by at least about 10% relative to a virus vector comprising a capsid protein that does not contain the deletion or substitution; or e) the capsid protein is serotype AAV1 and comprises a substitution of aspartic acid at position 5 of SEQ ID NO: 1, or is serotype AAV6, and comprises a substitution of aspartic acid at position 5 of SEQ ID NO: 6, wherein the capsid protein provides to an AAV vector comprising the capsid protein increased muscle transduction efficiency by at least about 10%, and further provides increased hepatic transduction efficiency, relative to a virus vector comprising a capsid protein that does not contain the substitution.