This is a breakout time in the development of nonviral gene therapy. It is both significant and exciting to see that nonviral delivery of mRNA by solid lipid nanoparticles (LNPs) has entered the accelerating phases of clinical applications due to the recent rollout of COVID-19 vaccines by Pfizer-BioNTech and Moderna, Inc. Other nonviral gene therapy strategies have also seen breakthroughs to treat various diseases on many forefronts. New and more efficient gene delivery technologies have been developed, including physical and mechanical methods, synthetic molecular conjugates/nanoparticles, and more recently, extracellular vesicle-based gene delivery.

Other technologies are under development. New and modified nucleic acid cargoes have been designed and utilized to increase the safety and efficiency of gene transfer and persistence of transgene expression. Furthermore, gene editing tools utilizing nonviral strategies can potentially bring safer and effective methods to treat genetic diseases.

The aim of this Special Issue is to provide a forum for researchers and clinicians dedicated to the investigations on the design of nonviral gene delivery technologies, vector development, as well as gene editing tools. In particular, new development in many new and existing technologies to treat diseases will be included. We welcome both original research and review articles that provide valuable insights into the design, production, and application of new or existing nonviral gene therapy for their application in treating diseases.

Potential topics include but are not limited to the following:

• Novel physical gene delivery strategies including electroporation, ultrasound-mediated gene delivery and hydrodynamics-based gene transfer
• Design and synthesis of molecular conjugates/nanoparticles including lipid nanoparticles, polymers, and other synthetic moieties-based gene transfer technologies
• Extracellular vesicles (including exosomes and other large vesicles)-based gene delivery
• Other nucleic acid-based gene transfer technologies
• Generation and optimization of nonviral cargoes including DNA, RNA and oligonucleotides
• Preclinical and clinical studies using nonviral gene transfer technologies in treating diseases
• Mechanistic studies following nonviral gene therapy
• Development of nonviral gene editing tools
• New nucleic acid modifications and formulations
• Cell therapy using nonviral delivery methods