About this Research Topic

Background

The possibility of inducing or suppressing the expression of specific genes with the targeted delivery of DNA or RNA molecules has developed in the last years into clinical approaches of gene therapy, to target the genetic component of various diseases, and most recently into new vaccination strategies for COVID-19. A major hurdle in the success of nucleic acid (NA) therapies or vaccines is their delivery to immune and non-immune cells. Naked, non-modified DNA and RNA molecules are inefficiently cross biological membranes, undergo rapid degradation and clearance, and may induce uncontrolled immune/inflammatory responses. To optimize efficacy and minimize side effects, recent research has focused on improving the design and delivery systems for NAs. A special focus on targeting immune cells is warranted in the case of vaccination, in order to shuttle the antigen-coding NAs to cells that will be able to synthesize, process, and present the antigen thereby triggering an optimally protective immune response. Likewise, the precise targeting of tumor-associated immune cells would allow for reprogramming of downregulated/blocked immune responses towards an efficient specific and innate anti-tumor immunotherapy.

NA delivery is mostly performed with viral vectors, highly efficient but with problems of immunogenicity and specificity of targeting. Among non-viral systems, Lipid Nanoparticles (LNPs) are currently the lead delivery systems for NA-based vaccines and therapeutics, whereas the recent development of NA nanoparticles (NANPs) has shown potential in enabling a regulated immunostimulation and delivery of scaffolded antigens. Major issues for NANPs and any old or new delivery systems are the efficient targeting of the specific cells, the efficiency of intracellular delivery, the capacity of escaping recognition by NA-specific pattern recognition receptors (PRRs) such as TLRs, NLRs, RIG-I, thereby preventing the activation of uncontrolled inflammatory responses.

In this Research Topic, we aim to provide an update on the development of innovative systems to deliver NAs to immune and non-immune cells. The Research Topic will cover the improvement of delivery systems to increase uptake by cells, reduce NA degradation, and control unwanted immunostimulation; the NA delivery for the treatment of various pathologies, including cancer, and for vaccination. Also, it is of particular interest to explore ways of NA delivery that can drive immune responses towards enhanced activity (e.g., in the case of cancer) or towards tolerance (e.g., in the case of autoimmune diseases).

The Topic will also discuss the current Food and Drug Administration (FDA)-approved delivery systems highlighted the success and failure of advanced TNA platforms, considering their commercialization potential.

We welcome the submission of Original Research, Review, and Mini Review, Methods, Clinical Trial articles covering, but not limited to, the following sub-topics:

- Development of novel carriers to deliver nucleic acids to immune and non-immune cells
- Design and formulation of delivery systems aiming at limiting NA recognition by PRRs and the ensuing unwanted immune/inflammatory responses
- Optimization of NA delivery systems and administration routes to enhance beneficial immunostimulation and immunogenicity or induce tolerance
- Improvement of delivery systems to increase uptake up by immune and non-immune cells and control NA stability and degradation
- Use of NAs as vaccines and for cancer/autoimmunity immunotherapy
- Use of novel technologies to improve the efficacy of NA delivery systems

Keywords: DNA, RNA, Nucleic Acids, NA, nucleic acid delivery, nucleic acid-based therapeutics, Lipid Nanoparticles, Nucleic acid nanoparticles, NANPs, Therapeutic Nucleic Acid, TNA, nanocarrier, vaccine, vaccine adjunct, cancer immunotherapy

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