Anchored lentiviral vector episomes for stem cell gene therapy in fanconi anemia

Santhosh Chakkaramakkil Verghese, Peter Kurre

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Fanconi anemia (FA) is an autosomal recessive, multisystem DNA repair disorder with prominent defects in the hematopoietic stem cell maintenance that result in the progressive attrition and failure in the early school age. Allogeneic stem cell transplantation has proved curative for patients with suitable donors. This, along with the characteristic survival advantage of phenotypically normal over non-corrected FA stem cells underscores the compelling rationale for stem cell gene therapy in the FA.While integrating lentiviral vectors (LV) have become the preferred platform for genetic correction in several hematologic and immunodeficiency disorders, the residual oncogenic potential by these vectors raises concerns in the FA stem cells about insertional mutagenic genetic lesions. On this backdrop, investigators are developing a new generation of non-integrating viral vectors capable of nuclear persistence through serial mitotic cycles and stable under selection to offset the comparatively lower transduction rates. Here, we review the competing approaches to develop such non-integrating lentiviral (NILV) episome vectors that faithfully replicate in the stem cells.

Original languageEnglish (US)
Pages (from-to)329-337
Number of pages9
JournalCurrent Gene Therapy
Volume16
Issue number5
DOIs
StatePublished - Oct 1 2016

Fingerprint

Fanconi Anemia
Cell- and Tissue-Based Therapy
Genetic Therapy
Plasmids
Stem Cells
Stem Cell Transplantation
Hematopoietic Stem Cells
DNA Repair
Maintenance
Research Personnel
Tissue Donors
Survival

Keywords

  • Fanconi anemia
  • Gene therapy
  • Hematopoietic stem/progenitor cells
  • S/MAR
  • Viral vectors

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

Cite this

Anchored lentiviral vector episomes for stem cell gene therapy in fanconi anemia. / Verghese, Santhosh Chakkaramakkil; Kurre, Peter.

In: Current Gene Therapy, Vol. 16, No. 5, 01.10.2016, p. 329-337.

Research output: Contribution to journalReview article

Verghese, Santhosh Chakkaramakkil ; Kurre, Peter. / Anchored lentiviral vector episomes for stem cell gene therapy in fanconi anemia. In: Current Gene Therapy. 2016 ; Vol. 16, No. 5. pp. 329-337.
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