UC San Diego

Nucleic acid therapeutics have emerged as a robust modality for the treatment of various diseases. However, a critical obstacle resides in the efficient and safe delivery of nucleic acids to their target sites, necessitating their delivery through complex extracellular and intracellular physiological barriers. Traditionally mammalian viruses have been the mainstay of nucleic acid delivery for biomedical applications, however, concerns surrounding immunogenicity and the potential for genomic integration have prompted several nascent research trajectories for alternative delivery platforms. Notably, advances in chemistry and bioengineering have yielded nonviral vectors comprising inorganic materials, peptides, lipids, and polymers. Nevertheless, these synthetic systems often fall short of replicating the gene transfer efficiency, expression duration, and specificity often achieved with viral counterparts. Recently, research has shifted toward the exploration of plant viruses, bacteriophages, and virus-like particles (VLPs) as innovative delivery platforms. These platforms, through the combination of advantageous features belonging to both viral and nonviral systems, present an exciting new methodology for nucleic acid delivery. This thesis seeks to explain the advantages of utilizing plant viruses and bacteriophages for nucleic acid delivery, emphasizing their potential to address prevailing delivery challenges, and provides a succinct overview of the current research developments in this rapidly changing field.