Novel compositions with tissue-specific targeting motifs and compositions containing same

Patent metadata

Field	Value
Publication number	US-2024024507-A1
Application number	US-202118255154-A
Country	US
Kind code	A1
Filing date	Dec 1, 2021
Priority date	Dec 1, 2020
Publication date	Jan 25, 2024
Grant date	—

Abstract

Provided herein are compositions including targeting peptides linked thereto or inserted in a targeting protein of a recombinant vector having at least one exogenous peptide comprising an amino acid sequence of N-x-(T/I/V/A)-(K/R) (SEQ ID NO: 47). Compositions providing such conjugates, targeting peptides, or recombinant vectors having a mutant capsid or envelope protein are provided as are uses thereof.

First claim

1 . A recombinant adeno-associated virus (AAV) particle (rAAV) having an AAV capsid comprising an amino acid sequence that comprises a motif N-x-(T/I/V/A)-(K/R) (SEQ ID NO: 47), wherein the amino acid sequence is part of at least the AAV vp3 protein in the AAV capsid, and wherein the rAAV comprises a vector genome packaged in the AAV capsid, wherein the vector genome comprises a nucleic acid sequence encoding a gene product under control of sequences which direct expression thereof, provided that the AAV capsid is not a mutant AAV2 capsid comprising an NDVRAVS (SEQ ID NO: 48) sequence.

2 . The rAAV of claim 1 , wherein the amino acid sequence comprising—the N-x-(T/I/V/A)-(K/R) motif is optionally flanked at the amino terminus and/or the carboxy terminus of the motif by two amino acids to seven amino acids, and is inserted into the AAV capsid vp3 region.

3 . The rAAV of claim 1 , wherein the motif sequence inserted into the AAV capsid comprises:

(a)

(SEQ ID NO: 40)

SSNTVKLTSGH;

(b)

(SEQ ID NO: 38)

EFSSNTVKLTS;

(c)

(SEQ ID NO: 46)

GGVLTNIARGEYMRGG;

(d)

(SEQ ID NO: 43)

GGIEINATRAGTNLGG;

(e)

(SEQ ID NO: 39)

GGSSNTVKLTSGHGG;

(f)

(SEQ ID NO: 42)

IEINATRAGTNL;

or

(g)

(SEQ ID NO: 41)

SANFIKPTSY.

4 . The rAAV of claim 1 , wherein the amino acid sequence of the motif is NTVK.

5 . The rAAV of claim 1 , wherein the motif N-x-(T/I/V/A)-(K/R) (SEQ ID NO: 47) is optionally flanked by two to seven amino acids at its carboxy- and/or amino terminus and inserted between amino acids 588 and 589 of an AAV9 capsid protein, based on the numbering of amino acid sequence: SEQ ID NO: 44.

6 . A composition comprising a stock of the rAAV of claim 1 and one or more of a physiologically compatible carrier, excipient, and/or aqueous suspension base.

7 . An endothelial cell targeting peptide, wherein the endothelial cell targeting peptide comprises a motif comprising an amino acid sequence of N-x-(T/I/V/A)-(K/R) (SEQ ID NO: 47) optionally flanked at the amino terminus and/or the carboxy terminus of the motif by two amino acids to seven amino acids, and optionally further conjugated to a nanoparticle, a second molecule, or a viral capsid protein.

8 . The endothelial cell targeting peptide of claim 7 , wherein the endothelial cell targeting peptide comprises:

(a)

(SEQ ID NO: 40)

SSNTVKLTSGH;

(b)

(SEQ ID NO: 38)

EFSSNTVKLTS;

(c)

(SEQ ID NO: 46)

GGVLTNIARGEYMRGG;

(d)

(SEQ ID NO: 43)

GGIEINATRAGTNLGG;

(e)

(SEQ ID NO: 39)

GGSSNTVKLTSGHGG;

(f)

(SEQ ID NO: 42)

IEINATRAGTNL;

or

(g)

(SEQ ID NO: 41)

SANFIKPTSY.

9 . The endothelial cell targeting peptide of claim 7 , wherein the amino acid sequence of the motif is NTVK.

10 . A composition comprising the endothelial cell targeting peptide of claim 7 and one or more of a physiologically compatible carrier, excipient, and/or aqueous suspension base.

11 . A fusion polypeptide or protein comprising a brain endothelial cell targeting peptide of claim 7 and a fusion partner which comprises at least one polypeptide or protein.

12 . A composition comprising a fusion polypeptide or protein of claim 11 and one or more of a physiologically compati

Assignees

• Univ Pennsylvania

Inventors

• Wilson James M
• Sims Joshua Joyner
• Yuan Yuan

Classifications

• A61K48/0041 Primary

  the non-active part being polymeric · CPC title

• C12N15/86 Primary

  Viral vectors · CPC title

• A61K39/42

  viral · CPC title

• A61K39/215

  Coronaviridae, e.g. avian infectious bronchitis virus · CPC title

• A61K38/1709

  from mammals · CPC title