Viral vector‐based gene therapies in the clinic

Abstract

Gene therapies are currently one of the most investigated therapeutic modalities in both the preclinical and clinical settings and have shown promise in treating a diverse spectrum of diseases. Gene therapies aim at introducing a gene material in target cells and represent a promising approach to cure diseases that were thought to be incurable by conventional modalities. In many cases, a gene therapy requires a vector to deliver gene therapeutics into target cells; viral vectors are among the most widely studied vectors owing to their distinguished advantages such as outstanding transduction efficiency. With decades of development, viral vector‐based gene therapies have achieved promising clinical outcomes with many products approved for treating a range of diseases including cancer, infectious diseases and monogenic diseases. In addition, a number of active clinical trials are underway to further expand their therapeutic potential. In this review, we highlight the diversity of viral vectors, review approved products, and discuss the current clinical landscape of in vivo viral vector‐based gene therapies. We have reviewed 13 approved products and their clinical applications. We have also analyzed more than 200 active trials based on various viral vectors and discussed their respective therapeutic applications. Moreover, we provide a critical analysis of the major translational challenges for in vivo viral vector‐based gene therapies and discuss possible strategies to address the same.

Current Status and Perspective on the Use of Viral-Based Vectors in Eukaryotic Microalgae

“…Updating the functions of viral genes and the genome composition is an important requirement for executing a rational design in which regulatory elements, such as promoters, terminators, or replication proteins, help reach strong GO expression. Finally, exploring the possibility of directly purifying recombinant proteins using elements from lytic viruses presents an alternative approach [ 177 ].…”

Revertant Mosaicism in Genodermatoses: Natural Gene Therapy Right before Your Eyes

“…Kim et al showed that in 2022, there were 19 ongoing therapeutic clinical trials with iPSC strategies, most of them being conducted in Japan (10 trials), but none were yet focused on skin diseases [ 129 ]. In addition, the iPSCs by Umegaki-Arao et al [ 126 ] and Tolar et al [ 67 ] were generated using retroviral vectors and therefore cannot be used in a clinical situation, as this strategy carries a risk of uncontrolled genomic integration [ 130 ]. Figure 4 summarizes the therapeutic approaches using revertant skin cells that have already been performed and the ones that may be pursued in the future.…”

An efficient rAAV vector for protein expression in cortical parvalbumin expressing interneurons

“…In addition, under favourable conditions most cells can be infected with rAAVs and express viral proteins 5 . Because of very low pathogenic risks, rAAVs are the main tool used in gene therapy clinical trials with several treatments approved both in Europe and USA 3 . Nevertheless, one of the major limiting factors in rAAV use is their low packaging capacity: at most 4–5 kb sequence can be inserted into the virus genome 1 , 6 .…”