Genome Engineering for Therapeutic Applications

Modern genome engineering technologies have made the targeted modification of human genes possible for a multitude of therapeutic applications. This chapter discusses the three main platforms that have been developed for targeting specific DNA sequences: zinc finger proteins, transcription activator-like effectors and, most recently, the CRISPR/Cas system. These technologies allow the rapid generation of custom genome engineering strategies aimed at treating a wide range of diseases from Duchenne muscular dystrophy to HIV infection to cancer. Synthetic nucleases based on these platforms have been used to facilitate targeted gene addition, correct disease-causing mutations, and create therapeutic gene knockouts. DNA-binding domains can also be linked to regulators of gene expression to create synthetic transcription factors. Targeted transcriptional activators have been employed to treat disease by upregulating compensatory genes or activating therapeutic targets, such as tumor suppressors. Synthetic repressors have been developed to treat dominant negative diseases and to silence oncogenes. With the potential to control the expression of any gene or modify any DNA sequence in the human genome, these technologies have immense potential to advance gene therapy and regenerative medicine.

Duke Scholars

Author Charles Gersbach Biomedical Engineering