Indian patent granted to THSTI
On 21st September 2021, an invention entitled APTAMER AGAINST M.TB HUPB AND USE THEREOF was granted for the term of 20 years from the 12th day of January 2017 in accordance with the provisions of the Indian Patents Act,1970. This invention pertains to Dr. Tarun Sharma, Senior Research scientist, THSTI and Dr. Jaya S. Tyagi AIIMS-New Delhi.
This patent is based on the invention of DNA aptamers against HupB, a proteinthat play a vital role in Mycobacterium tuberculosis (MTb) biology. The entry and survival of MTb
within host cells is orchestrated partly by an essential histone-like protein HupB (Rv2986c). Despite being an essential drug target, the lack of structural information has impeded the development of inhibitors targeting the indispensable and multifunctional C-terminal domain (CTD) of HupB. To bypass the requirement for structural information in the classical drug discovery route, Dr. Sharma in collaboration with Prof. Jaya S. Tyagi generated a panel of DNA aptamers against HupB protein through Systemic Evolution of Ligands by EXponential (SELEX) enrichment. Two G-quadruplex-forming high-affinity aptamers (HupB-4T and HupB-13T) were identified, each of which bound two distinct sites on full-length HupB..While HupB-4T robustly inhibited DNA-binding activity of HupB in vitro, both the aptamers recognized surface-located HupB and significantly blocked Mtb entry into THP-1 monocytic cells (p < 0.0001). These DNA aptamers block DNA-binding activity of HupB, inhibit virulent Mtb infection in host cells, and demonstrate aptamers to be inhibitors of HupB functions. Successful delivery of these aptamers in M.tb using appropriate vehicles (egliposomes) may lead to their application as a therapeutic agent for M.tb.