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Review
. 2014 May;3(5):636-42.
doi: 10.5966/sctm.2013-0206. Epub 2014 Mar 28.

Concise review: lessons learned from clinical trials of gene therapy in monogenic immunodeficiency diseases

David A Williams  1 , Adrian J Thrasher
Affiliations
Review

Concise review: lessons learned from clinical trials of gene therapy in monogenic immunodeficiency diseases

David A Williams et al. Stem Cells Transl Med. 2014 May.

Abstract

Thirty years ago, retroviral transfer of genetic material into hematopoietic stem and progenitor cells (HSC/Ps) led to predictions that this technology would transform modern medicine [Nature 1983;305:556-558; Nature 1984;310:476-480]. Studies in several immunodeficiency diseases in the past 15 years have demonstrated clear proof of principle that gene therapy can have long-lasting, potentially curative effects without the need to search for allogeneic donors and without risk of graft-versus-host disease. Improvement in gene transfer efficiency for target HSC/Ps brought to light issues of insertional mutagenesis caused by transfer vectors, resulting in oncogene transactivation and leukemias. Lessons from these adverse events have now led to a new generation of vectors, refinements in conditioning regimens, and manufacturing, which are paving the way for expanded applications of the current technology and recent emphasis on gene targeting/genome editing as the next advancements in the field.

Keywords: Clinical trials; Gene therapy; Hematopoietic cells; Immunodeficiency; Progenitor cells.

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