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Fetal gene therapy

Gene Therapy volume 6, pages 1200–1201 (1999)Cite this article

Somatic gene therapy is currently focused on the introduction of genetic material into non-germline cells with the goal of correcting a human disease. Over 300 clinical protocols have been approved for the use of gene therapy in children and adult patients. The recent application of two protocols based on the prenatal treatment of α-thalassemia and severe combined immunodeficiency (SCID)1 now raises issues regarding the feasibility of fetal or in utero gene therapy. Recent advancements in prenatal diagnosis of genetic disease, fetoscopic technique, and fetal transplantation, no longer pose significant technical hurdles for in utero clinical testing.2 Ideally, in utero gene transfer embodies the ‘raison d’être’ for the gene therapy field – the correction and prevention of disease. Inherited disorders such as cystic fibrosis, Tay-Sachs disease, and a variety of hematopoietic stem cell disorders (sickle cell, thalassemia) could potentially be ameliorated or cured before birth.

Arguments for the use of fetal directed gene transfer include fewer number of target cells needed for correction, hence less vector needed. Rapid expansion of fetal stem cell populations suggests that ex vivo transduction of fetal cord blood may be more efficient than adult hematopoietic cells. The presumed immunologic tolerance during fetal development to viral vectors or transgene products may not limit gene transfer effectiveness. The immaturity of blood–brain barrier may allow for greater ease of treating CNS disease.3 The enhanced proliferative/regenerative capacity of fetal tissue assumes that fetal cells may be inherently more ‘transducible’ than adult cells.

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  1. Rm 7101 Thurston Building, UNC Gene Therapy Center, CB#7352, Chapel Hill, 27599, NC, USA

    Christopher E Walsh MD PhD

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  1. Christopher E Walsh MD PhD
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Walsh MD PhD, C. Fetal gene therapy. Gene Ther 6, 1200–1201 (1999). https://doi.org/10.1038/sj.gt.3300991

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