Today (April 25th) is DNA Day, commemorating the date in 1953 when James Watson, Francis Crick, Maurice Wilkins, Rosalind Franklin and colleagues published the discovery of the double helix structure of DNA. Their work underpins the pioneering development of a new area of genetic medicines – therapies that use the transfer of DNA and/or RNA to modify gene expression.
The ability of the therapeutic DNA to cross the different biological barriers to reach the target compartment within the cell (e.g. cytosol or nucleus) is relatively poor. Hence, the development of drug delivery vectors from non-viral or viral sources became critical to unlock and exploit the full potential of therapeutic DNA and other nucleic acids such as RNAs. The role of the vector is to protect the nucleic acid cargo from premature degradation and facilitate it reaching the target site of action within the cells. Once the vector, with its cargo, has successfully crossed the relevant biological barriers, the cargo must then be released intact at appropriate concentrations to exert the desirable therapeutic response. Other critical considerations include colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, adequate loading efficiency. Viral vectors such as Adeno-associated viruses (AAVs) are the most common platform for delivering nucleic acids with commercial approval of various products including Imlygic® in 2015 and Luxturna® in 2018. Alternatively, non-viral vectors are used for forming complex medicines and they are currently receiving a surge in interest, potentially due in part to the recent approval of two mRNA-based vaccines (Comirnaty® (Pfizer-BioNTech) and Spikevax® (Moderna)) developed in the fight against the global COVID-19 pandemic, whereby a synthetic version of the mRNA encoding the SARS-CoV-2 spike protein is encapsulated within lipid nanoparticles (LNPs).
SEDA’s team of experts has direct experience of supporting several nanomedicine and other complex delivery systems into preclinical and clinical development. SEDA have played a pivotal role in design and development of drug delivery technologies including but not limited to peptidic, polymeric, inorganic and hybrid nanoparticles, for the targeted delivery of nucleic acids and other synthetic small molecules and peptides. We have established a network of experts in the diverse array of advanced characterisation techniques that are so vital to success in this field. Our experiences of interactions with various global regulatory authorities are invaluable in guiding the phase appropriate characterisation required for QC release and product performance understanding of nanomedicines for our Clients. Development is undertaken with a line of sight to the commercial product, with manufacturability, scalability, and patient acceptability being key drivers.
Our in-house DMPK and Clinical Pharmacology capability, together with close alliances to other non-clinical and clinical experts are ideal for ensuring the seamless communication required to maximise success of complex medicines, where minor changes in formulation or manufacturing process can have major impact on biodistribution (and hence safety/efficacy).
Find out more about our Complex Medicines capabilities and the expertise we can offer.