Methods and compositions for gene inactivation

• US 20100111907A1
• Filed: 10/15/2009
• Published: 05/06/2010
• Est. Priority Date: 05/25/2006
• Status: Abandoned Application

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Biosciences, Inc. (Sangamo Therapeutics, Inc.)
• Inventors: Holmes, Michael C., Ando, Dale, Lee, Gary Ka Leong
• Application Number:
  US12/587,995
• Publication Number:
  US 20100111907A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10345 Special targeting system for viral vectors
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113

Abstract

Disclosed herein are methods and compositions for inactivating CCR-5 genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs, such as adenovirus (Ad) vectors, and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

Claims

1. A method for inactivating an HIV receptor gene in a subject, the method comprising:

introducing, into a cell of the subject, a homing endonuclease that binds to a target site in an HIV receptor gene and cleaves the HIV receptor gene.

2. The method of claim 1, wherein the homing endonuclease is engineered to bind to the target site in the HIV receptor gene.

3. The method of claim 1, wherein a polynucleotide encoding the meganuclease is introduced into the cell.

4. The method of claim 1, wherein the homing endonuclease is introduced into the cell ex vivo.

5. The method of claim 1 wherein the homing endonuclease is introduced into the cell in vivo.

6. The method of claim 3, wherein the homing endonuclease is introduced into the cell ex vivo.

7. The method of claims 3, wherein the homing endonuclease is introduced into the cell in vivo.

8. The method of claim 1, wherein the HIV receptor is a CCR-5 receptor.

9. The method of claim 1, wherein the HIV receptor is a CXCR4 receptor.

10. The method of claim 2 wherein the cell is selected from the group consisting of a stem cell, a T-cell, a macrophage, a dendritic cell and an antigen-presenting cell.

11. The method of claim 1, wherein the homing endonuclease is selected from the group consisting of I-SceI, I-CeuI, PI-PspI, PI-Sce, I-SceIV, I-CsmI, I-PanI, I-SceII, I-PpoI, I-SceIII, I-CreI, I-TevI, I-TevII and I-TevIII.

12. The method of claim 9, wherein the homing endonuclease is SceI or CreI.

13. A method of treating or preventing HIV infection in a subject, the method comprising:

inactivating an HIV receptor according to the method of claim 1 in a cell isolated from the subject; and

introducing the cell into the subject.

14. A method of treating or preventing HIV infection in a subject, the method comprising:

introducing the polynucleotide encoding the meganuclease according to claim 7 into a subject; and

inactivating an HIV receptor.