# US 12,758,653 B2 · Lentiviral vectors in hematopoietic stem cells to treat X-linked chronic granulomatous disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,758,653 B2 - Document ID: US12758653B2 - Status: Granted - Kind: B2 - Application number: 17/775,857 - Filed: 2020-11-12 - Published: 2022-12-01 - Granted: 2026-10-13 - Earliest claimed: 2019-11-12 - Assignees: The Regents of the University of California - Applicants: The Regents of the University of California - Inventors: Donald B. Kohn; Ryan L. Wong; Roger Paul Hollis - Web page: https://patentgrep.com/patent/US12758653B2 ## CPC - A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered} - A61P 37/00: Drugs for immunological or allergic disorders - C12N 9/0036: {acting on NADH or NADPH (1.6)} - C12N 15/86: Viral vectors - A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid} - C12N 2740/16043: viral genome or elements thereof as genetic vector - C12N 2800/22: Vectors comprising a coding region that has been codon optimised for expression in a respective host - C12N 2830/008: cell type or tissue specific enhancer/promoter combination - C12N 2830/48: regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE - C12Y 106/03001: NAD(P)H oxidase (1.6.3.1), i.e. NOX1 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Y: ENZYMES ## Abstract Described herein is a lentiviral vector (LV) for the treatment of X-linked chronic granulomatous disease (X-CGD). The vector comprises an expression cassette comprising a nucleic acid construct comprising a CYBB promoter or effective fragment thereof, and a nucleic acid that encodes gp91phox operably linked to the CYBB promoter or promoter fragment thereof. ## Claims ### Claim 1 A recombinant lentiviral vector (LV) comprising: an expression cassette comprising a nucleic acid construct comprising: a CYBB promoter or effective fragment thereof; and a nucleic acid that encodes a Gp91phox operably linked to said CYBB promoter or promoter fragment thereof; wherein said CYBB promoter or effective fragment thereof comprises the nucleic acid sequence of SEQ ID NO: 3; and wherein said expression cassette further comprises regulatory nucleic acid sequences comprising enhancers consisting of SEQ ID NO: 6 and SEQ ID NO: 11 for expression of the nucleic acid that encodes the Gp91phox operably linked to said CYBB promoter. ### Claim 2 (depends on 1) The vector of claim 1, wherein said vector shows high expression in CD33+ (bulk myeloid cells), high expression in CD19+ B cells, high expression in CD66b+CD15+CD11b+CD16+ (mature neutrophils), and low or no expression in CD3+ T cells. ### Claim 3 (depends on 1) A host cell transduced with a vector of claim 1. ### Claim 4 (depends on 3) The host cell of claim 3, wherein: said cell is a stem cell; and/or said cell is a stem cell derived from bone marrow, and/or from umbilical cord blood, and/or from peripheral blood; and/or said cell is a human hematopoietic progenitor cell; and/or said cell is a human hematopoietic progenitor cell that is a CD34+ cell. ### Claim 5 (depends on 1) A method of treating a chronic granulomatous disease (X-CGD) in a subject, said method comprising: transducing a stem cell and/or progenitor cell from said subject with a vector of claim 1; and transplanting said transduced cell or cells derived therefrom into said subject where said cells or derivatives therefrom express said Gp91phox. ### Claim 6 (depends on 5) The method of claim 5, wherein: said cell is a stem cell; and/or said cell is a stem cell derived from bone marrow; and/or said cell is a human hematopoietic stem and progenitor cell; and/or said cell is a human hematopoietic stem and progenitor cell that is a CD34+ cell. ### Claim 7 A recombinant lentiviral vector (LV) comprising SEQ ID NO: 22. ### Claim 8 (depends on 7) The vector of claim 7, wherein said vector shows high expression in CD33+ (bulk myeloid cells), high expression in CD19+B cells, high expression in CD66b+CD15+CD11b+CD16+ (mature neutrophils), and low or no expression in CD3+ T cells. ### Claim 9 (depends on 7) A host cell transduced with a vector of claim 7. ### Claim 10 (depends on 9) The host cell of claim 9, wherein: said cell is a stem cell; and/or said cell is a stem cell derived from bone marrow, and/or from umbilical cord blood, and/or from peripheral blood; and/or said cell is a human hematopoietic progenitor cell; and/or said cell is a human hematopoietic progenitor cell that is a CD34+ cell. ### Claim 11 (depends on 7) A method of treating a chronic granulomatous disease (X-CGD), in a subject, said method comprising: transducing a stem cell and/or progenitor cell from said subject with a vector of claim 7; and transplanting said transduced cell or cells derived therefrom into said subject where said cells or derivatives therefrom express said Gp91phox. ### Claim 12 (depends on 11) The method of claim 11, wherein: said cell is a stem cell; and/or said cell is a stem cell derived from bone marrow; and/or said cell is a human hematopoietic stem and progenitor cell; and/or said cell is a human hematopoietic stem and progenitor cell that is a CD34+ cell.