Gene Modification Therapies for Hereditary Diseases in the Fetus

The study reviews the feasibility of intrauterine gene modification therapy (IUGT) for treating hereditary diseases. Both gene addition and gene editing approaches have successfully increased normal protein production to reverse or arrest pathology in utero. Different viral vectors, including lentiviral, adenoviral, and adeno-associated viral vectors, have been used to deliver the therapeutic transgene efficiently. Non-viral lipid nanoparticles have also shown promise. The success of IUGT depends on sustained therapeutic transgene expression, silencing of transgene expression, neutralizing antibodies, growth of transduced cells, and pre-existing cellular damage. Long-term postnatal surveillance is necessary to assess safety and potential risks, such as cell and genome toxicity, oncogenic potential, immune responsiveness, and germline mutation.