Anchored Lentiviral Vector Episomes for Stem Cell Gene Therapy in Fanconi Anemia

Author(s): Santhosh Chakkaramakkil Verghese, Peter Kurre

Journal Name: Current Gene Therapy

Volume 16 , Issue 5 , 2016

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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.

Keywords: Fanconi anemia, Hematopoietic stem/progenitor cells, Gene therapy, Viral vectors, S/MAR.

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Article Details

Year: 2016
Published on: 08 February, 2017
Page: [329 - 337]
Pages: 9
DOI: 10.2174/1566523217666170113165407
Price: $65

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