Rewriting the Genetic Code: The History and Impact of Gene Editing

Abstract

Abstract Gene editing technologies have evolved significantly over the past few decades, revolutionising biomedical research and therapeutics. Initially, restriction enzymes provided researchers with basic tools for deoxyribonucleic acid (DNA) manipulation. However, the advent of engineered nucleases, such as zinc finger nucleases (ZFNs) and transcription activator‐like effector nucleases (TALENs), marked significant advancements for more precise and customisable genome modifications. The discovery of CRISPR–Cas9 further transformed gene editing, offering a more efficient, cost‐effective and versatile approach. The success of CRISPR in transgenic mouse generation and clinical trials is a testament to this. However, challenges such as off‐target effects, immunogenicity and ethical concerns surrounding germline editing and eugenics remain. This review will discuss the discovery, mechanisms and applications of gene editing tools as they have evolved. It will also introduce modern iterations of gene editing to tackle off‐target effects and the ethical responsibility that comes with it. Key Concepts Gene editing has evolved from restriction enzymes to programmable nucleases capable of precise genome modifications. Zinc finger nucleases were the first major platform for targeted DNA cleavage but came with technical challenges. Transcription activator‐like effector nucleases (TALENs) improved gene editing through simpler and more predictable DNA sequence recognition. CRISPR–Cas9 transformed gene editing by using guide RNA to direct efficient, low‐cost and scalable DNA targeting. Off‐target mutations, delivery barriers and immune responses remain major technical challenges for therapeutic gene editing. Newer iterations of the CRISPR–Cas system offer higher fidelity gene editing and applications beyond DNA cleavage. Germline editing, mosaicism, eugenics and informed consent remain central ethical concerns in gene editing.