Anchored Lentiviral Vector Episomes For Stem Cell Gene Therapy In Fanconi Anemia.

Anchored Lentiviral Vector Episomes For Stem Cell Gene Therapy In Fanconi Anemia. Curr Gene Ther. 2017 Jan 13; Authors: Verghese SC, Kurre P Abstract Fanconi anemia (FA) is an autosomal recessive¬, multisystem DNA repair disorder with prominent defects in hematopoietic stem cell maintenance that result in their progressive attrition and failure in 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 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 FA stem cells with potentially preexisting 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 stem cells. PMID: 28093967 [PubMed - as supplied by publisher]
Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research