CD25 preselective anti-HIV vectors for improved HIV gene therapy

Stefanos Kalomoiris, Je'Tai Lawson, Rachel X. Chen, Gerhard Bauer, Jan Nolta, Joseph S Anderson

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy of HIV gene therapies. Here we describe the development of preselective anti-HIV lentiviral vectors that allow for the purification of vector-transduced cells to achieve an enriched population of HIV-resistant cells. A selectable protein, human CD25, not normally found on CD34+ hematopoietic progenitor cells (HPCs), was incorporated into a triple combination anti-HIV lentiviral vector. Upon purification of cells transduced with the preselective anti-HIV vector, safety was demonstrated in CD34+ HPCs and in HPC-derived macrophages in vitro. Upon challenge with HIV-1, improved efficacy was observed in purified preselective anti-HIV vector-transduced macrophages compared to unpurified cells. These proof-of-concept results highlight the potential use of this method to improve HIV stem cell gene therapy for future clinical applications.

Original languageEnglish (US)
Pages (from-to)366-375
Number of pages10
JournalHuman gene therapy methods
Volume23
Issue number6
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Applied Microbiology and Biotechnology
  • Genetics(clinical)
  • Genetics
  • Pharmacology

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