Current Stem Cell Reports

, Volume 4, Issue 1, pp 52–60 | Cite as

In Utero Gene Therapy and Genome Editing

  • Heather A. Hartman
  • Avery C. Rossidis
  • William H. Peranteau
Prenatal Therapies (WH Peranteau, Section Editor)
  • 25 Downloads
Part of the following topical collections:
  1. Topical Collection on Prenatal Therapies

Abstract

Purpose of Review

The purpose of this review is to summarize the current status of in utero gene therapy and postnatal in vivo genome editing with an eye toward prenatal genome editing.

Recent Findings

The rational for gene therapy and genome editing in utero is described, specifically the small size of the fetus, fetal immunologic immaturity, prenatal accessibility of stem and progenitor cells, and the ability to treat target diseases prior to birth. We review studies in normal and disease small and large animal models which demonstrate the feasibility and safety of in utero gene therapy using a variety of viral vectors. Postnatal in vivo genome editing with CRISPR-Cas9 in a number of murine disease models is discussed including the preference for nonhomologous end-joining compared to homology-directed repair in non-proliferating adult cells as a potential benefit to application of CRISPR-Cas9 genome editing to the fetus. Finally, the ethical challenges of human in utero gene therapy are discussed in the context of the EVERREST trial that is currently being designed.

Summary

In utero gene therapy and genome editing is a developing field with great potential to treat congenital monogenic diseases. More research in small and large animal models is required before clinical translation can occur.

Keywords

Gene therapy Gene editing CRISPR-Cas9 Fetus In utero 

Notes

Compliance with Ethical Standards

Conflict of Interest

Heather A. Hartman, Avery C. Rossidis, and William H. Peranteau declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Heather A. Hartman
    • 1
  • Avery C. Rossidis
    • 1
  • William H. Peranteau
    • 1
  1. 1.The Center for Fetal ResearchThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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