From Bench to Bedside: The Evolution of Human Genome Editing in Clinical Practice

Abstract

Genome-editing is a precise technology used to insert, delete, replace or modify a specific DNA sequence, and also used for epigenome and gene regulation. The haploid human genome (23 chromosomes) is about 3 billion base-pairs long and contains 20,000–25,000 distinct protein-coding genes. Genome-editing tools include meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems. Genome-editing technology is mostly used in research and ongoing clinical trials to diagnose and treat certain conditions including hematologic disorders, cancers and infectious diseases. There are some technical challenges, safety and bioethical concerns that limit routine clinical applications of genome-editing technologies. However, quality control measures are being developed to minimize off-target effects, DNA-damage toxicity and immunotoxicity, improve delivery methods and editing-efficiency, and thus provide more precise, more efficient and safer editing tools