Internal medicine

Mitochondrial DNA

Disease

Bioinformatics

Biology

Gene

Germline

Genetic enhancement

Germline mutation

Mutation

Computational biology

Genetics

Medicine

Nature Medicine

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. Germline gene therapy has the potential to prevent inheritance of monogenic disorders but must first be optimized for accuracy.

Principles of and strategies for germline gene therapy