Fetal gene therapy The window of opportunity for fetal gene therapy

Serious consideration of somatic gene therapy for the fetus arises from the ability to diagnose a number of diseases early in fetal life and from recent advances in gene transfer techniques. Fetal gene therapy offers the ability to target pluripotential cells that will generate a stable population of corrected cells, to initiate gene therapy before the disease becomes manifest, to avoid morbidity and mortality that may normally occur during the perinatal or early postnatal period and, in the case of the lung, to disperse the gene therapy reagent with relative ease by diffusion in a fluid-filled structure rather than across an air-liquid interface. Recent studies in sheep, rats, and mice have demonstrated that adenoviral or retroviral vectors can transfer gene expression in the fetus and neonate (Holzinger et al, 1995; McCray et al, 1995; Pitt et al, 1995; Vincent et al, 1995). As pointed out by Pitt and Robbins (1996), such studies indicate the feasibility of gene therapy as a clinical treatment. However, the duration of gene expression in these studies has been short. Inflammatory, immunological and other factors limited the duration of gene expression. The possibility exists that gene therapy, initiated earlier in development and before inflammatory and immune mechanisms mature, would lengthen the duration of gene expression and limit the adverse responses to subsequent treatments. Thus, one goal of future studies is to define potential 'windows of opportunity' for initiating gene therapy before inflammatory and immune responses develop.