IP Library › Granted Patent US 12,692,518
Granted Patent B2
US 12,692,518 · App. 18/296,235 · Granted Jul 28, 2026

Therapeutic genome editing in Wiskott-Aldrich syndrome and x-linked thrombocytopenia

Inventors: David J. Rawlings (Seattle, WA); Iram Khan (Issaquah, WA)
Assignee: Seattle Children's Hospital
C12N15/907C12N9/22
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Quick Facts
Patent No.
US 12,692,518
App. No.
18/296,235
Filed
Apr 5, 2023
Granted
Jul 28, 2026
Kind
B2
Art Unit
1646
USPC
435/462
Abstract

Described herein are systems and methods for treating, inhibiting, or ameliorating X-linked disorders including Wiskott-Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate WAS or XLT. The systems include nuclease and vector donor constructs configured for co-delivery to modify endogenous WAS locus.

Claims (22)

1 . A method of modifying a cell, comprising introducing into a cell:

(a) a Cas nuclease or a nucleic acid encoding the Cas nuclease, wherein the Cas nuclease is capable of cleaving a Wiskott-Aldrich Syndrome (WAS) locus in a cell genome;

(b) a guide RNA (gRNA), wherein the gRNA is encoded by a nucleotide sequence set forth in any one of SEQ ID NOs: 31-34; and

(c) a vector comprising a WAS gene or portion thereof.

2 . The method of claim 1 , wherein the nuclease comprises a Cas9 nuclease.

3 . The method of claim 1 , wherein the vector is an adeno-associated viral (AAV) vector.

4 . The method of claim 1 , wherein the vector comprises a WAS cDNA.

5 . The method of claim 4 , wherein the vector lacks a promoter operably linked to the WAS cDNA.

6 . The method of claim 4 , wherein the WAS cDNA is inserted into a first exon of a WAS gene.

7 . The method of claim 1 , wherein the vector comprises an enhancer.

8 . The method of claim 1 , wherein the vector comprises a nucleic acid homologous to the WAS locus.

9 . The method of claim 1 , wherein the cell is selected from a T cell or a hematopoietic stem cell (HSC).

10 . The method of claim 9 , wherein the cell is a CD34+ HSC.

11 . The method of claim 1 , wherein the cell is obtained from a human male subject.

12 . A cell prepared by the method of claim 1 .

13 . A method of treating, inhibiting or ameliorating Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT) in a subject, comprising: administering the cell of claim 12 to the subject.

14 . The method of claim 13 , wherein the cell is autologous to the subject.

15 . The method of claim 1 , wherein the gRNA is encoded by the nucleotide sequence of SEQ ID NO: 31.

16 . The method of claim 1 , wherein the gRNA is encoded by the nucleotide sequence of SEQ ID NO: 32.

17 . The method of claim 1 , wherein the gRNA is encoded by the nucleotide sequence of SEQ ID NO: 33.

18 . The method of claim 1 , wherein the gRNA is encoded by the nucleotide sequence of SEQ ID NO: 34.

19 . The method of claim 13 , wherein the subject is male.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 25, 2026
From: RAWLINGS, DAVID J.; KHAN, IRAM
To: SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE)
Reel/Frame 075088/0904 →
Continuity (3)
Continuation 16605748 · Apr 19, 2018
Provisional Application 62488249 · Apr 21, 2017
Related Publication 20240141389A1 · May 2, 2024
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