Award details

DNA-based therapies to combat antibiotic resistance on pathogenic bacteria

Reference	BBS/E/J/000CA327
Principal Investigator / Supervisor	Professor Mervyn Bibb
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	38,373
Status	Completed
Type	Institute Project
Start date	01/10/2007
End date	30/09/2008
Duration	12 months

Abstract

The Enterprise Fellowship supports the establishment of a spin out from the John Innes Centre focus on the pressing need to combat the rise of infectious diseases caused by multi drug resistant (MDR) bacteria. We are pioneering a novel and proprietary DNA-based therapy, transcription factor decoys (TFDs), to be used in combination with extant antibiotics to reduce the resistance to them encountered in the clinic and so increase their efficacy and shelf life. TFDs (which are distinct from antisense molecules) represent a new paradigm for the development of therapeutics: they are oligonucleotides incorporating specific sequences known to interfere with transcription factors in order to manipulate gene expression, as such they have the following advantages: designed by a rational process; can be cheaply manufactured at scale; low toxicity; greatly reduced R&D expenditure, as all stages of conventional drug development (target identification, lead compound discovery, medicinal chemistry) are truncated. We are to take the novel approach of using DNA-based therapies to resensitize the pathogenic bacteria to existing antibiotics. We have adapted the transcription factor decoy (TFD) approach (pioneered in eukaryotes) to bacteria to prevent the expression of the resistance mechanism and filed for protection around the concept, tools and materials derived. Decoys are short oligonucleotides capable of interacting with targeted transcription factors in a highly specific fashion to switch off genes determining resistance. TFDs are a powerful new class of therapeutics that are rationally designed (based on sequence information), easy to produce and stable and have low toxicity profiles. These properties mean that the path from lead compound (designed bioinformatically) to drug candidate (chemical synthesis) is truncated with substantial efficiencies projected for both R&D cost and development time. Used in combination with the antibiotic our TFDs are capable of restoring its clinical efficacy and tackle this serious issue for public health. In addition it would be expected to rescue the sales of current antibiotics and extend their useful shelf life potentially beyond the expiry of their original patent.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	Microbiology, Pharmaceuticals, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search