Engineered muscle targeting compositions
AssigneesThe Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of Technology
InventorsPardis Sabeti, Mohammadsharif Tabebordbar, Simon Ye, Kim Lagerborg, Alexandra Stanton, Amy Wagers
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Abstract
Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.
Claims12
A composition comprising
- a modified AAV capsid polypeptide comprising a targeting moiety effective at targeting a muscle cell,
- wherein the targeting moiety is inserted after any one of amino acids 453, 587, and 588 of an AAV9 VP1 capsid polypeptide,
- wherein the targeting moiety comprises one or more n-mer motifs,
- each n-mer motif consisting of an amino acid sequence of
- Xm1 RGD X1X2X3X4,
- Xm2Xm1 RGD X1X2X3X4, or
- Xm3Xm2Xm1 RGD X1X2X3X4,
- wherein X1, X2, and X3 are independently selected from any amino acid, X4 is L or T, and
- (i) Xm3 and Xm2 are independently selected from any amino acid, and Xm1 is G, S, T, N, V, R, I, K, or A, or
- (ii) Xm3 and Xm1 are independently selected from any amino acid, and Xm2 is N, S, A, P, T, M, or D, or
- (iii) Xm2 and Xm1 are independently selected from any amino acid, and Xm3 is T, N, S, A, G, D, or E.
An engineered particle, comprising a modified AAV capsid polypeptide comprising a targeting moiety effective at targeting a muscle cell,
- wherein the targeting moiety is inserted after any one of amino acids 453, 587, and 588 of an AAV9 VP1 capsid polypeptide, or any combination thereof, or into an analogous position of an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or AAV rh.10 VP1 capsid polypeptide
- wherein the targeting moiety comprises one or more n-mer motifs,
- each n-mer motif consisting of an amino acid sequence
- Xm1 RGD X1X2X3X4,
- Xm2Xm1 RGD X1X2X3X4, or
- Xm3Xm2Xm1 RGD X1X2X3X4,
- wherein X1, X2, and X3 are independently selected from any amino acid, X4 is L or T, and
- (i) Xm3 and Xm2 are independently selected from any amino acid, and Xm1 is G, S, T, N, V, R, I, K, or A, or
- (ii) Xm3 and Xm1 are independently selected from any amino acid, and Xm2 is N, S, A, P, T, M, or D, or
- (iii) Xm2 and Xm1 are independently selected from any amino acid, and Xm3 is T, N, S, A, G, D, or E.
Dependencies are inferred from the claim text.