RNA-based therapy to protect the lungs and kidneys from COVID-19

FIRST LINE OF DEFENCE: Design and implementation of a novel RNA-based therapy to protect the lungs and kidney against coronavirus infections

The SARS-CoV-2 virus responsible for the current COVID-19 pandemic is well-established to infect the lungs, thereby oftentimes triggering severe pneumonia. In addition, it is now becoming increasingly clear that the virus also infects the kidneys amongst hospitalised patients, resulting in impaired kidney function and, in severe cases, irreversible kidney damage or even organ failure. Awaiting the development of effective vaccines, both the general public as well as patients that are severely affected by COVID-19 (or future coronavirus pandemics) could greatly benefit from anti-viral medications that specifically target the virus and effectively lower viral infection. Such therapeutic approaches will protect the integrity of vital organs.

In a strategic alliance between the LUMC-based Departments of Internal Medicine (Clinical Application and Nephrology) and Medical Microbiology (Coronavirus biology) and the Leiden-based SME Hybridize Pharma (RNAbased therapeutics), the aim is to develop short RNA-nucleotide sequences (called antisense oligonucleotides or commonly known as ASOs) that are complementary to regulatory sequences of COVID-19. Hereafter, it will be tested how effective individual ASOs are in reducing lung and kidney cell infection by COVID-19 in vitro. Finally, lead candidate ASOs will be administered to the lungs (via aerosols) or the kidneys (intravenously) and tested for tissue uptake, pharmacokinetics and toxicity in vivo. When successful, Hybridize Pharma will guide the transition from the pre-clinical to clincal arena for ASOs that are effective in combatting COVID-19 in close collaboration with the LUMC.

Summary
The SARS-CoV-2 virus contains conserved short genomic sequences essential for viral replication. The aim is to develop short RNA-nucleotide sequences complementary to these regulatory sequences and thereby inhibit viral replication. These tools will confer clinicians with a first line of defense to protect the lungs and kidneys against the deleterious effects of COVID-19 and future coronavirus infections.
Technology Readiness Level (TRL)
2 - 4
Time period
18 months
Partners