Current State of Human Gene Therapy: Approved Products and Vectors

Abstract

In the realm of gene therapy, a pivotal moment arrived with Paul Berg’s groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause—the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich assortment of 16 drugs, from siRNA, miRNA, and CRISPR/Cas9 to DNA aptamers and TRAIL/APO2L, as well as 46 carriers, from AAV, AdV, LNPs, and exosomes to naked mRNA, sonoporation, and magnetofection. The article also discusses the advantages and disadvantages of each product and vector type, as well as the current challenges faced in the practical use of gene therapy and its future potential.

Patient derived model ofUBA5-associated encephalopathy identifies defects in neurodevelopment and highlights potential therapies

“…Indeed, we observed overexpression of UBA5 at 9 days following SINEUP application, with >3.5 fold increase. It would be beneficial to explore delivery of SINEUP via other delivery methods including adeno-associated virus and lipid nanoparticles ( 89–92 ). These delivery vehicles do not allow for genome integration and have been approved for human trials by the FDA ( 89–92 ).…”

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

“…The EAA showed high binding affinity to different exosomes and enabled efficient loading of nucleic acid drugs on exosomes without complicated conjugation or modification, which providing a generalizable strategy for further developing exosomes-based delivery vehicles of nucleic acid drugs [ 415 ]. Interestingly, in addition to acting as guiding ligands, aptamers themselves have been explored as therapeutic acids which attracting much research interest [ 416 ]. Two aptamers targeting β-catenin and NF-κB were connected to construct artificial circular RNAs (acircRNAs) [ 417 ].…”

Recent advances of engineered oncolytic viruses-based combination therapy for liver cancer

“…Since then, many clinical programs have been launched worldwide. Gene therapy depends on appropriate gene delivery vectors because deoxyribonucleic acid and small interfering RNA (siRNA) can be easily degraded in vivo, and they must remain stable in host cells to exert therapeutic effects, which require effective transmembrane delivery vectors [ 5 ]. Selecting a suitable delivery vector will enable nucleic acid molecules to reach their action sites, improve delivery efficiency, exert anti-cancer effects, and reduce damage to normal tissues and organs [ 6 ].…”