METHOD AND ANTISENSE COMPOSITION FOR SELECTIVE INHIBITION OF HIV INFECTION IN HEMATOPOIETIC CELLS

• US 20080187993A1
• Filed: 11/15/2007
• Published: 08/07/2008
• Est. Priority Date: 10/23/2003
• Status: Abandoned Application

• Current Assignee: Avi Biopharma, Inc.
• Original Assignee: Avi Biopharma, Inc.
• Inventors: Iversen, Patrick L., Mourich, Dan V., Bestwick, Richard K.
• Application Number:
  US11/940,987
• Publication Number:
  US 20080187993A1
• Time in Patent Office: Days
• US Class Current: 435/375
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 2319/10 containing a tag for extracellular membrane crossing, e.g. TAT or VP22
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2810/6054 Retroviridae

Abstract

A method and conjugate for selectively targeting activated hematopoietic cells, e.g., macrophage or T-lymphocyte cells, are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against HIV, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into activated, HIV-infected cells, e.g., activated, HIV-infected macrophage and T-lymphocyte cells. An exemplary embodiment of the invention provides an antisense compound directed to the HIV Vif gene, causing the production of defective HIV virions in an infected individual.

Claims

1. A method of achieving selective uptake of a substantially uncharged antisense compound into activated human macrophage or T lymphocyte cells, comprising

(a) exposing a population of human macrophage or T lymphocyte cells that include activated human macrophage or T lymphocyte cells to an rTAT-antisense conjugate composed of (i) the antisense compound and (ii) covalently coupled thereto, a reverse TAT (rTAT) polypeptide having the sequence identified as SEQ ID NO:

1; and

(b) by said exposing, achieving a greater level of intracellular uptake of the oligonucleotide analog into activated macrophage or T-lymphocyte cells than is achieved (i) by exposing non-activated macrophage or T-lymphocyte cells to the same antisense conjugate, or (it) by exposing activated macrophage or T-lymphocyte cells to the antisense compound in the absence of the rTAT polypeptide.