Current Advances in the Safety, Efficiency and Targeted Delivery of Gene Editing Tools

About this Research Topic

Background

Advances in gene editing has allowed us to perform targeted modifications in the genome for treating diseases. Programmable nucleases, such as CRISPR/Cas9, have contributed to an accessible and efficient editing of the genome of living organisms, including eukaryotic and mammal cells. Progress of viral and non-viral vector delivery platforms have increased the likelihood of achieving targeted gene editing. Targeted gene editing without unneeded consequences is challenging and there is scope of further improvement.

Viruses have been repurposed into viral vectors as a tool for gene delivery. The most frequently used are lentiviral vectors (LV) and adeno associated viruses (AAV). Derived from human viruses, they allow efficient gene transfer into mammalian cells and with their modified viral envelopes (pseudotyping) they can improve their tropism for different primary cell types.

These gene delivery platforms, especially viral vectors, suffer from risks such as genotoxicity and immunotoxicity. Non-viral vectors carrying gene editing tools, including plasmid DNA, gRNA, mRNA, ribonucleoproteins (RNP), etc. are expected to resolve some of these challenges. There has been a great amount of work in recent years validating a variety of non-viral delivery systems, including liposomes and lipid nanoparticles (LNPs), polymeric nanoparticles, gold nanoparticles, virus-like particles (VLP), exosomes, extracellular vesicles (EVs), inorganic materials, and smart hydrogel systems.

Temporal and spatial control of gene editing is desirable to increase safety for gene editing based treatment strategies. Significant progress has been made to localize the expression and delivery of gene editing molecules to the cells and organs of interest. However, it is still challenging to limit the gene editing outcomes to target cell types and organs. This series specifically focuses on highlighting new methodologies and research to achieve gene editing to the target organs and cell-types.

The aim of this Research Topic is to cover novel delivery mechanisms of genome editing tools into target cell types and tissues, as well as trends for safe and efficient gene editing strategies. Covered areas can include, but are not limited to:

• Ex vivo or in vivo delivery techniques for genome editing tools
• Applications of novel delivery methods in therapy
• Novel targeted gene editing and delivery platforms and materials
• Viral vectors with reduced risk for immune reactions and genotoxicity
• Lipid nanoparticles gene editing platforms
• Synthetic polymers for gene delivery
• New methods to reduce off-target editing
• Refinements and development of safe and novel gene editing platforms, including homology-directed repair, base editing and prime editing

Keywords: CRISPR/Cas9; non-viral vectors; Gene editing Gene therapy; primary cells, nanoparticles, Base editing, Prime editing

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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