971620Bacterial Cell Targeted RNA TherapeuticsClosedSmall Business Research InitiativeInnovate UKThere is intense global interest in the area of AMR, with multiple international players. The widespread use of conventional/traditional antibiotics has led to the increasing emergence of multiple drug-resistant pathogenic bacteria. In the last 20 years there has been no new development of new drugs for Gram-negative infections and there is an urgent need to develop alternative therapeutic strategies to reduce the morbidity and mortality associated with bacterial infections. The objective of the project is to evaluate and advance a novel and revolutionary technology for the delivery of drug candidates that target Gram-negative bacterial infection-related RNAs and generate a new class of non-conventional precision medicines. The project will involve demonstrating both an in vitro and in vivo Proof of Concept against targets that may include LpxC, mcr-1, acpP and ClpX using antisense oligonucleotides/siRNA/synthetic RNA silencers. To overcome the poor uptake efficiency of antisense oligonucleotides into bacteria and deliver an optimal bacteria targeted RNA therapeutic to the market, Pedanius Therapeutics is utilising groundbreaking and validated porin translocation technology (Antibiotic Assisted Translocation Platform, AATP) to develop RNA therapeutics that target bacterial cells of interest and facilitate the uptake and internalisation of an antisense oligonucleotide/siRNA/ synthetic RNA silencer payload. Should the AATP technology be able to deliver the antisense oligonucleotides into Gram-negative bacteria, it will have the potential to address the AMR crisis, since resistance mechanisms for conventional antibiotics apparently have no effect on antisense antimicrobials as proposed in this project. And as antisense antimicrobials are a platform technology in itself, they can be rapidly designed and synthesised to target any microbe in a significant reduced drug discovery time.