SirgaAB has versatile, high through-put screens for selecting small molecules that interfere with unique and critical functions of RNA in controlling gene expression in infectious and non-infectious diseases.
At this time, SirgaAB is seeking financial support for proof-of-concept in the use of its screening technologies, the selection of small molecules that interfere with a unique, and critical functions of RNA in Gram-positive pathogens and retroviruses.
The screens are designed to select small molecule, candidate drugs that interfere with a target RNA function in control of gene expression and viral replication. These particular screens are designed for the proof-of-concept program and for which a provisional patent has been submitted, will select candidate drugs that interfere with RNA/RNA and RNA/protein interactions unique to Gram-positive bacteria and to retroviral replication and critical to the organism. These RNA/RNA and RNA/protein interactions do not occur in the human host.
The need for new antibiotics and anti-viral drugs is evident, especially against single and multi-drug resistant bacterial pathogens and retroviruses. To a fault, the competition in seeking such drugs has targeted ribosome-mediated protein synthesis (traditional antibiotic target), enzymes (proteins) and structures (cell wall) that are readily altered by variant strains of the organism, thus creating resistance even to these new drugs.
In contrast, the targets for which the proposed screens have been designed, exploit a novel functions, involves RNA chemistry and structure, and a unique control of gene expression and viral replication. Importantly, the organism's ability to develop resistance to a drug interfering with this function will be extremely difficult due to the fundamental nature of the targeted interactions.
The screens have been proven in vitro to mimic the RNA functions. The specificity, and flexibility of the screens have been demonstrated. The screens' sensitivity and high through-put potential as a fluorescence-based, microtiter plate assay have been demonstrated. Initial studies of the bacterial target design are published, Nelson et al., 2006, RNA 12, 1254-1261. Thus, in both screens critical RNA function has been reduced to a biochemical size that can be readily studied with biochemical and biophysical techniques. Initial development of the microplate-based screen has been successful, and transfer to a robotic high through-put screen is envisioned.