Nanoparticles for the Delivery of RNA-Based Therapeutics

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Background

RNA-based therapeutics represent an exciting and growing field of research, yet a still modestly exploited frontier in gene therapy, as technical difficulties affecting their in vivo delivery have limited their clinical application in the past two decades. RNA-based gene therapy is potentially more versatile than DNA-based therapy, as it allows the targeting of not only any protein-coding gene, but also regulatory sequences, and may permit a finer modulation of gene expression. On the other hand, in order to develop therapeutic formulations, functional RNA molecules need to be chemically or enzymatically modified in order to ensure their stability towards degradation by nucleases and reduced immunogenicity. Complexing with different lipids/lipid nanoparticles may further protect them from degradation, and allows adding features such as targeting moieties. With the optimization of delivery systems for small RNAs, the field is now expanding rapidly. In contrast, there are still several technical issues that need to be overcome for the delivery of long RNAs, such as synthetic mRNAs and regulatory long non-coding RNAs (lncRNAs).

New biocompatible nanocarriers suitable for RNA-based therapeutics need to be developed. Such delivery systems will have to confer to the RNA cargo resistance to nucleases, but also have an efficient cellular uptake and preservation of its functional secondary folding and 3D structure. Moreover, they have to be non-cytotoxic nor immu-nogenic, and they should guarantee a correct sub-cellular localization, and possibly be able to target cell-specifically. These features may be obtained by a smart combination of nanoparticle-based delivery systems with chemical modifications of RNA. In case of regulatory ncRNAs, the design of the RNA molecule will also have to be optimized, in order to preserve its active structure and the accessibility of the functional RNA domains.

This Research Topic will focus on novel nanocarriers for the delivery of nucleic acids therapeutics and RNA-based therapeutics in particular, such as (but not limited to) various types of organic nanoparticles, nanomi-celles, and hollow-core nucleic acid nanospheres, with special emphasis on the delivery of medium and long RNA molecules (such as ncRNAs and mRNAs).

All issues connected to the delivery of RNA-based therapeutics may be addressed in this Topic, covering subjects ranging from the biodistribution of the nanocarrier, its stability and half-life, its cell-specific targeting, cellular uptake, sub-cellular localization, to its metabolism and toxicology. Considering the specificities of RNA drugs, it will be particularly important to integrate considerations regarding the design of both the nanocarrier (cargo capacity, maximum length of the RNA molecule, possible intracellular release of the RNA) and of the synthetic RNA molecule, including its 3D functional structure and the steric accessibility of the active regions.

Important Note: All submissions/contributions to this Research Topic must be in line with the scope of the journal/section they are submitted to. While authors are encouraged to draw from other disciplines to enrich their papers where relevant, they must ensure papers fall within the scope of the journal/section, as expressed in its mission statement.

We would like to acknowledge Dr. Elsa Zacco as the Co-ordinator for this Research Topic.

Dr. Paola Valentini holds patents on nucleic acids and nanoparticles and Dr. Loris Rizzello holds patents on biomaterials, drug delivery and nanobiotechnology. All other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: RNA-Based Therapeutics, Drug Delivery, Nanocarrier, Non-Coding RNAs, Chemical Modifications

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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