IFIT Polypeptides and uses for treating tuberculosis

Interferon Induced proteins with Tetratricopeptide repeats (IFIT) proteins are a family of antiviral proteins have been shown to confer immunity against viral infection. IFIT proteins have been shown to be conserved in vertebrates, with homologues having been identified in several organisms. These proteins are generally produced during viral infection, Interferon (IFN) treatment and during pathogen recognition by the immune system. The mechanism of action of these proteins has been extensively studied during the course of viral infection. IFIT1 consequently inhibits the translation or replication of the non-self RNA in an organism. IFITs are known to prevent viral replication by binding and controlling the function of viral proteins and RNAs, but their role against bacteria is not well understood. The role of IFITs in the anti-mycobacterial response of macrophages and other immune cells has not been described previously. The present invention relates to methods of increasing the cellular concentration of Interferon Induced Protein with Tetratricopeptide repeats (IFIT) polypeptides in a cell infected with a mycobacterium. The method involves the introduction of exogenous IFIT polypeptides or expression vectors encoding the exogenous IFIT polypeptides or mRNA into the cell, wherein increasing the cellular concentration of the IFIT polypeptide reduces the number of viable mycobacteria in the cell.

The biotech industry involved in drug development can partner to develop this invention. Since it will be in the best interest of humanity to eradicate the scourge of tuberculosis any new effective therapy will be required by all governments to acquire therapies that limit the development of drug resistance. All public and private health institutions will welcome the potential economic benefits to mankind by limiting the detrimental health consequence of any disease such as tuberculosis. These institutions include the following:

• Public and Private Hospitals
• International and National tuberculosis control programs
• National Health Ministries

Patients that suffer from tuberculosis world-wide will benefit from this invention. New antituberculosis drugs directed towards the mycobacteria directly have a high risk for the development of resistance by the pathogen. Host directed therapies clearly have a much lower risk and are clearly more suitable as a sustainable therapy for infectious diseases. Numerous host-directed therapies are being investigated with various cytotoxic risk levels. The aim will be to develop a host-directed therapy with the least risk of an overblown inflammatory response and least potential to exacerbate other existing genetic, metabolic and infectious disorders. To achieve the former the immune response that is elicited must not be broad based but very specific to minimize other non-specific effects. The current invention in development is envisaged to be very specific with minimal risk of complications in relation to other medical conditions.

Dr Bienyameen Baker, Department of Biomedical Sciences, Stellenbosch University.

Dr Abhilahsa Madhvi Mishra (Past PhD student) Department of Biomedical Sciences, Stellenbosch University.