Research

Life Sciences & Biotechnology

Title :

G-Quadruplex forming DNA Aptamers against human EGFR as an alternative therapeutic approach for epidermal carcinomas

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Krishna Kishore Nampudi, All India Institute Of Medical Sciences, New Delhi

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

The project aims to develop G-quadruplex forming DNA aptamer inhibitors to target the ectodomain of Epidermal Growth Factor Receptor (sEGFR), an established drug target in epidermal origin cancers like head and neck, breast, colon, ovary, and lung cancers. The recombinant sEGFR will be expressed and purified using the Baculovirus expression system. Purified protein will be used as a target for aptamer selection to fish out the high-affinity aptamers from the G-quadruplex biased library. The SELEX process will be used to identify G-quadruplex DNA aptamers, as they are stable and have a higher tolerance to the nucleases. Binding studies of the identified aptamers will be carried out with recombinant sEGFR protein using SPR & ITC to determine their binding affinity. Further, using cell viability assays, identified aptamers potency will be tested against EGFR overexpressed human epidermoid carcinoma cells, A431. Based on the molecular and cellular results, identified aptamers-based inhibitors will be modified to improve their efficacy if required. The project would provide a novel class of inhibitors to treat EGFR overexpressed cancers. The proposal's outcome will have a significant impact in the area of aptamer-based therapeutics, as aptamers are known to have high specificity and lower toxicity.

Total Budget (INR):

39,36,196

Organizations involved