Nucleic acid-based therapeutics (NTAs) hold strong potential against modern diseases. They have the ability to target protein non-coding genes and transcripts, have high specificity and durable effects. With technology improvements, the number of approved TNA-drugs is increasing but clinical translation is restricted by their suboptimal delivery in vivo. The “TNA-delivery challenge” is caused by their large size and negative charge, and by their susceptibility to enzymatic degradation in the body. Extracellular vesicles (EVs) answer the TNA-delivery challenge. Here, researchers from Erasmus MC together with experts from ExoVectory and Getinge join efforts and know-how to develop novel therapeutic bioengineered extracellular vesicles as a powerful new delivery modality with enhanced therapeutic load and improved delivery, optimize their bioproduction, and perform a proof-of-concept study for PCa treatment.
Each year 12000 Dutch men are diagnosed with PCa. Sadly, over 3000 develop lethal disease despite treatment. There is a lot to gain in terms of better treatment, i.e. longer life with better quality for more men with PCa.
EVs are small cell bubbles naturally produced in the body that function as DNA and RNA carriers between cells. EVs possess therapeutic capacity: they can cross biological barriers; target and enter specific cells; and are “stealthy” to the recipient’s immune system. Clinical trials show that EVs are bio-safe, have low immunogenicity and cannot trigger neoplastic transformation. This renders EVs our preferred choice of a TNA delivery system.
Within this project we will produce and test an experimental proof-of-concept formula: bioengineered extracellular vesicles for the intracellular delivery of therapeutic nucleic acids (TNA) to suppress the growth of prostate cancer cells. Our novel technology will pave the road to a new anticancer modality and enable the further maturation of nucleic acid-based therapeutics to ultimately create impact in the combat against PCa and other cancers.