About this Research Topic
The increasing level of knowledge re the genetic basis of disease has opened up the potential to modulate gene expression for therapeutic purposes. A range of nucleic acids including antisense oligonucleotides, siRNA, pDNA, mRNA and CRISPR have the capacity to achieve gene replacement, gene silencing and gene editing. The main challenge to translating these concepts into the clinic is the design and manufacture of effective and safe non-immunogenic delivery systems. Such delivery systems must be be stable during manufacture and in vivo administration and must be capable of prolonged exposure coupled with tunable biodistribution to disease sites beyond the liver.
The target for this issue is 'non-viral formulations for oral delivery of therapeutic nucleic acids (NA)'. Until recently most NA medicines on the market were viral-based products. However, recently several NA products using lipid nanoparticles were approved by the FDA and the EMA spearheading a heighthened level of interest in the advantages and flexibility of these technologies. The products include siRNA for liver disease (Patisiran) marketed by Alnylam and the 2 mRNA vaccines by Pfizer and Moderna. The breakthrough of these products has increased confidence in the technology due to the impressive efficacy and safety data produced particularly by the Covid 19 vaccines. The demand for such products is likely to increase due to the development of new viral strains and the potential for NA to treat a wider range of diseases beyond prophylactic vaccines and liver disease. To date these products are for parenteral administration and due to the well know advantages of the oral route it seems obvious that an investigation of this non-invasive route should be explored for NA therapeutics. In addition, oral administration also presents the opportunity for local delivery to the gut wall for IBD or intestinal cancer thus avoiding the extra burden of achieving systemic availability.
Scope of the research topic is wide. Submissions covering the full lifecycle from the design of the target product profile to selection of excipients, formulation of the product, characterisation and pre-clinical evaluation will be considered. Specifically assessment of the barriers to oral delivery including physicochemical and biological challenges; methods to overcome these barrier including novel formulations and delivery devices. Critical debate on the feasibility of translating therapeutic NA into viable oral medicines and the clinical benefits of same.
The development and evaluation of new biomaterials will be particularly welcome. In addition challenges for manufacturing, quality, stability/shelf life and scale-up will also be included. Submissions discussing the regulatory requirements for these new therapies including debates on the need for new tools to make regulatory assessment and approval more efficient. Novel assessment tools including: 3D GUT models, in silico modeling etc.
Types of manuscripts could include:
Position/opinion papers from clinicians, industry and/or regulators
Research papers on the topic outlined above
Keywords: siRNA, mRNA, nanomedicine, bio-materials, lipis, polymers, local delivery, IBD, intestinal cancer, manufacturing, scale-up, regulatory hurdles
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