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Prospects for Prenatal Gene Therapy

  1. Charles Coutelle

Published Online: 17 FEB 2014

DOI: 10.1002/9780470015902.a0025275

eLS

eLS

How to Cite

Coutelle, C. 2014. Prospects for Prenatal Gene Therapy. eLS. .

Author Information

  1. Imperial College London, London, UK

Publication History

  1. Published Online: 17 FEB 2014

Abstract

Somatic prenatal gene therapy (PGT) aims at treatment/prevention of progressive tissue/organ damage in early-manifesting life-threatening and otherwise incurable genetic diseases. Preclinical investigations applying different vectors and transgenes on several animal models including nonhuman primates have shown PGT to provide better access to target cells and their progenitors, induce tolerance to vector/transgenic protein and reduce the required amount of vector in comparison to postnatal gene therapy. Human application of PGT is now technically possible, however, safety issues regarding potential adverse effects on fetal development, oncogenesis-induction and germline transmission as well as ethical considerations concerning risk–benefit assessment and alternative reproductive choices have so far prohibited human trials. Increasing the safety profile, for example, by use of novel vector systems and long-time primate safety/efficiency studies, may prospectively validate PGT for selected human applications. High standards regarding information given to prospective patients (informed consent) and to the public on the aims, benefits and remaining risks will play an important role in any future clinical application of PGT.

Key Concepts:

  • Somatic gene therapy addresses genetic diseases of the treated individual at the level of the molecular defect.

  • Prenatal gene therapy of early onset genetic disease prevents irreparable damage to tissues and organs and induces postnatal tolerance to therapeutic transgenic proteins.

  • Prenatal gene delivery can reach proliferating precursor cell compartments more effectively than postnatal gene therapy.

  • Different animal models including models of human genetic disease are required to establish optimal vectors and routes for gene delivery including those applicable in humans, to demonstrate the therapeutic efficiency of the delivered gene therapy, and to monitor and investigate the occurrence of potential adverse effects.

  • In utero gene therapy could provide an alternative to termination of pregnancy or acceptance of an affected child after prenatal diagnosis of a genetically affected fetus, or to in vitro fertilisation followed by embryo selection in families with preconceptional knowledge of a specific genetic risk.

  • Current options to avoid birth of a genetically affected child (termination of pregnancy, preimplantation diagnosis/embryo selection) impose very high demands on the outcome of human prenatal gene therapy with respect to its level of safety and effectiveness.

  • Ethical considerations regarding the assessment and communication of the risks and benefits of prenatal gene therapy and its perception by affected families, the medical profession and the general public will play an important part in decisions on the clinical application of this novel therapeutic approach.

Keywords:

  • prenatal (fetal, in utero) gene therapy;
  • prenatal diagnosis of;
  • genetic disease;
  • fetal development;
  • gene therapy vectors;
  • animal models;
  • oncogenesis;
  • germline gene transfer;
  • targeted gene correction (genome editing);
  • immune tolerance;
  • ethical considerations