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Principles of and strategies for germline gene therapy

Abstract

Monogenic disorders occur at a high frequency in human populations and are commonly inherited through the germline. Unfortunately, once the mutation has been transmitted to a child, only limited treatment options are available in most cases. However, means of correcting disease-causing nuclear and mitochondrial DNA mutations in gametes or preimplantation embryos have now been developed and are commonly referred to as germline gene therapy (GGT). We will discuss these novel strategies and provide a path forward for safe, high-efficiency GGT that may provide a promising new paradigm for preventing the passage of deleterious genes from parent to child.

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Competing interests

S.M. is a co-founder and shareholder of Mitogenome Therapeutics, Inc. The other authors declare no competing financial interests

Correspondence to Shoukhrat M. Mitalipov.

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Fig. 1: Embryo selection following PGD for families in which one parent carries an autosomal dominant mutation.
Fig. 2: Possible repair outcomes in embryos homozygous for a germline mutation in the MYBPC3 gene.
Fig. 3: Repair outcomes in embryos heterozygous for a germline mutation in the MYBPC3 gene41.