CRISPR Advancements for Human Health

Abstract

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has emerged as a powerful gene editing technology that is revolutionizing biomedical research and clinical medicine. The CRISPR system allows scientists to rewrite the genetic code in virtually any organism. This review provides a comprehensive overview of CRISPR and its clinical applications. We first introduce the CRISPR system and explain how it works as a gene editing tool. We then highlight current and potential clinical uses of CRISPR in areas such as genetic disorders, infectious diseases, cancer, and regenerative medicine. Challenges that need to be addressed for the successful translation of CRISPR to the clinic are also discussed. Overall, CRISPR holds great promise to advance precision medicine, but ongoing research is still required to optimize delivery, efficacy, and safety.

Figure 1

Traditional CRISPR-Cas9 genome editing. The sgRNA contains a scaffold structure that complexes to the Cas9 protein and also includes a uniquely engineered segment that can be designed to direct the Cas9 protein to a specific DNA sequence of interest. Once bound to the DNA at the target location, the Cas9 protein creates a double-stranded break in the DNA. The cell naturally heals this double-stranded break using one of two main repair mechanisms. Non-homologous end joining (NHEJ) is the most common mechanism typically resulting in indel formation. Homology-directed repair (HDR) is a less efficient repair mechanism that allows for introduction of exogenous DNA through the use of a donor DNA repair template.

Figure 2

Expanding CRISPR toolbox. CRISPR-based genome editing technologies are rapidly progressing. CRISPRa and CRISPRi can be used to recruit transcription factors for increased gene expression or repressors for decreasing gene expression. Base editors have been designed to convert C-to-T or A-to-G nucleotide substitutions without creating a double-stranded break in the DNA. Prime editing includes a small, engineered segment of new sequence that is used for precisely repairing the DNA after a single-stranded nick has been generated. Continued advancement of CRISPR-based tools will help drive the next generation of precise, versatile and deliverable genome editing tools.