Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases

Abstract

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentiviral), electroporation techniques, and virus-like particles (VLPs), which facilitate precise editing of target cells in vivo or ex vivo. These delivery platforms have enabled promising early-phase clinical trials demonstrating feasibility, safety, and durable gene modification in patient populations. For example, LNPs have been pivotal in delivering mRNA editors for liver-targeted metabolic diseases. At the same time, viral vectors have been used for ex vivo modification of T cells and hematopoietic stem cells in autoimmune and infectious diseases. Despite encouraging results, challenges remain in optimizing delivery specificity, minimizing off-target effects, and ensuring long-term safety and efficacy. Ongoing and upcoming trials continue to refine these delivery technologies and expand the therapeutic reach of gene editing.

Keywords: CRISPR-Cas9; MT: RNA/DNA editing; base editors; delivery systems; gene editing; gene therapy; precision medicine.

Graphical abstract

Figure 1

Evolution of CRISPR technology A timeline illustrating key milestones in the development of CRISPR, from the discovery of repetitive DNA sequences to genome editing breakthroughs, variant development, and ongoing ethical and regulatory considerations.

Figure 2

Mechanism of CRISPR-Cas9 gene editing The Cas9-sgRNA complex induces a double-stranded break at a target DNA site, which is repaired either by error-prone non-homologous end joining (NHEJ), causing insertions or deletions, or by precise homology-directed repair (HDR) using a donor DNA template.