Perspectives on gene therapy for Fanconi anemia

Abstract

Introduction: Fanconi anemia (FA) is a rare inherited disease characterized by congenital abnormalities, bone marrow failure (BMF) and cancer predisposition. Although allogeneic hematopoietic stem cell transplantation (HSCT) is the preferential therapy for restoring the bone marrow (BM) function of FA patients, gene therapy represents a new alternative in FA.

Areas covered: This review covers the areas of gene therapy with γ-retroviral and lentiviral vectors. Additionally, the perspectives of gene editing and cell reprogramming for the gene therapy of FA are discussed.

Expert opinion: Currently, there is no clinical evidence showing that gene therapy can restore the BM function of FA patients. However, improvements in vector development and advances in manipulation of hematopoietic stem cells (HSCs) have resulted in gene therapy progresses, opening new perspectives for the treatment of FA patients. Although, in FA patients, reduced HSC numbers will be available for gene correction and autologous transplantation, a strong selective advantage is expected from corrected FA HSCs. This suggests that limited numbers of corrected HSCs could be sufficient to rescue the hematopoiesis of FA patients. In addition to ex vivo gene therapy, significant advances have been achieved in in vivo gene therapy and also in the fields of gene targeting and cell reprogramming, with a potential role in the future treatment of FA.

Keywords:

• advanced therapies
• cell reprogramming
• Fanconi anemia
• gene editing
• gene therapy
• hematopoietic stem cell transplantation
• stem cells

Acknowledgments

This paper is dedicated to the memory of David Frohnmayer, the cofounder, with his wife, Lynn, of the Fanconi Anemia Research Foundation. The authors are deeply indebted to the FA families who are always collaborating to help in FA research and to Aurora de la Cal, the secretary of the Spanish Association for Fanconi Anemia.

Declaration of interest

Current work at the Division of Hematopoietic Innovative Therapies in the field of FA is supported by grants from the European Commission’s Seventh Framework Program (http://ec.europa.eu/research; FP7 GA 222878, PERSIST; HEALTH-F5-2012-305421, EUROFANCOLEN), the Spanish Ministry of Economy and Competitiveness (SAF2012-39834), the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (RETICS RD12/0019/0023; PI08/0701) and the Dirección General de Investigación de la Comunidad de Madrid (CellCAM; Ref S2010/BMD-2420). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

Notes

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