Center for Fetal Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Curr Opin Obstet Gynecol. 2023 Apr 1;35(2):134-139. doi: 10.1097/GCO.0000000000000854.
The development of modern gene editing tools alongside promising innovations in gene sequencing and prenatal diagnostics as well as a shifting regulatory climate around targeted therapeutics offer an opportunity to address monogenic diseases prior to the onset of pathology. In this review, we seek to highlight recent progress in preclinical studies evaluating the potential in-utero gene editing as a treatment for monogenic diseases that cause morbidity or mortality before or shortly after birth.
There has been significant recent progress in clinical trials for postnatal gene editing. Corresponding advances have been made with respect to in-utero cell and enzyme replacement therapies. These precedents establish the foundation for 'one-shot' treatments by way in-utero gene editing. Compelling preclinical data in liver, pulmonary and multisystemic diseases demonstrate the potential benefits of in-utero editing approaches.
Recent proof-of-concept studies have demonstrated the safety and feasibility of in-utero gene editing across multiple organ systems and in numerous diseases. Clinical translation will require continued evolution of vectors and editing approaches to maximize efficiency and minimize unwanted treatment effects.
现代基因编辑工具的发展，以及基因测序和产前诊断方面的有前景的创新，加上靶向治疗的监管环境的转变，为在病理学发生之前解决单基因疾病提供了机会。在这篇综述中，我们旨在强调最近在临床前研究中评估在宫内基因编辑作为治疗在出生前或出生后不久导致发病或死亡的单基因疾病的潜力方面取得的进展。
产后基因编辑的临床试验取得了重大进展。在宫内细胞和酶替代疗法方面也取得了相应的进展。这些先例为通过宫内基因编辑进行“一次性”治疗奠定了基础。在肝脏、肺部和多系统疾病中具有说服力的临床前数据表明了宫内编辑方法的潜在益处。
最近的概念验证研究表明，在多个器官系统和多种疾病中，宫内基因编辑具有安全性和可行性。临床转化将需要继续改进载体和编辑方法，以最大限度地提高效率并最小化不必要的治疗效果。
