Advances in CRISPR therapeutics

This Review focuses on the potential applications of CRISPR to treat diseases that cannot be overcome by inducing frameshifts or premature stops in coding genes. The authors discuss Cas protein engineering and CRISPR systems beyond Cas9 that create a toolbox to engineer the human genome. The clustered regularly interspaced short palindromic repeats (CRISPR) renaissance was catalysed by the discovery that RNA-guided prokaryotic CRISPR-associated (Cas) proteins can create targeted double-strand breaks in mammalian genomes. This finding led to the development of CRISPR systems that harness natural DNA repair mechanisms to repair deficient genes more easily and precisely than ever before. CRISPR has been used to knock out harmful mutant genes and to fix errors in coding sequences to rescue disease phenotypes in preclinical studies and in several clinical trials. However, most genetic disorders result from combinations of mutations, deletions and duplications in the coding and non-coding regions of the genome and therefore require sophisticated genome engineering strategies beyond simple gene knockout. To overcome this limitation, the toolbox of natural and engineered CRISPR-Cas systems has been dramatically expanded to include diverse tools that function in human cells for precise genome editing and epigenome engineering. The application of CRISPR technology to edit the non-coding genome, modulate gene regulation, make precise genetic changes and target infectious diseases has the potential to lead to curative therapies for many previously untreatable diseases.

Automated summary

This review focuses on the potential applications of CRISPR technology in treating diseases that are not easily overcome by traditional gene knockout methods. The authors discuss how Cas protein engineering and the development of CRISPR systems beyond Cas9 have expanded the toolbox for engineering the human genome. CRISPR has been used to knockout harmful mutant genes, fix errors in coding sequences, and has the potential to become a curative therapy for previously untreatable diseases through precise genome editing and epigenome engineering.