The primary objective of our group is to perform a complete end-to-end research for bringing a select number of protein-based biotherapeutics (biosimilar, biobetters and/or novel molecules) from a laboratory set-up to the market. Based on the disease prevalence, both globally and in the Indian context, our research will focus on developing biologics to treat cancer, rheumatoid arthritis, and childhood bronchiolitis. Efforts are ongoing to develop biosimilars of (a) adalimumab (Humira, an anti-TNF monoclonal antibody), used for treatment of rheumatoid arthritis, and (b) human Granulocyte-Colony Stimulating Factor (hG-CSF), widely used to prevent and treat chemotherapy-induced neutropenia. Our preliminary studies on the biosimilar of Humira produced by single cell clone have indicated biosimilarity with the originator molecule. In the case of hG-CSF, we are in the process of examining the biological activity and in vivo half-life of engineered versions of the G-CSF, and securing the intellectual property rights for these inventions.
Metabolics Focus Area
Iron Deficiency Anemia Solutions via Microbial Engineering Technology [IDEAS MEET]
The activities of this unit are geared for achieving the national goals of Swast Nagrik, Swast Bharat, and Saksham Bharat.
Iron deficiency is a major worldwide health problem and oral iron supplementation remains the mainstay for its effective treatment. Unfortunately after almost five decades of this approach India still tops the list of nations with most anemic women and children. The need of the hour is to develop an arsenal of choices for providing low cost mass scale iron amelioration in large segments of the population fully keeping in mind local social and cultural sensibilities. Besides providing better iron supplementation products, efforts also have to focus on improving the bioavailability of supplemented iron, as well as, iron trapped within the different tissue compartments. To achieve this goal our group is focusing on the following strategies:
1. Development of organic/bio-molecules that would specifically increase sequestered iron release from ferritin and to disrupt hepcidin-ferroprotin interaction and also explore for natural agents that can enhance the expression of divalent metal transporter 1 (DMT1), erythropoietin and also improve trafficking of iron containing molecular complexes across enterocytes. The goal is to enhance effective enterocyte iron absorption and preventing loss of iron trapped in senescent enterocytes.
2. Mapping alterations in gut microflora that impact upon iron absorption capabilities utilizing next generation sequencing technology with an ultimate goal of identifying putative bacterial species that may be exploited as potential probiotic candidates for enhancing iron absorption and also countering the side effects of conventional oral iron supplementation therapy.
3. Develop oral iron supplements utilizing GRAS compliant scaffolds that can be produced at low cost via mass production by microbial technology/fermentation processes.
4. Screening Herbal/Microbial extracts as a source of heme iron [SatVik heme Nutraceuticals]
The major share of the biotherapeutic market belongs to the monoclonal antibodies (mAbs) and recombinant proteins. In recent years, we have established a platform for therapeutic human mAbs production using suspension CHO cells. Various steps, including cloning of genes, transfection procedures, lab scale-up procedure to achieve high yielding single cell producers, and biophysical characterization of purified mAbs for their biosimilarity, have been optimized. In addition, we have also created polyethylene glycol (PEG) derivatives and novel variants of G-CSF using semi-rational protein evolution approaches. By employing mRNA engineering, we have improved the yield of hG-CSF production from E. coli.
The group already has considerable expertise in the area of cellular iron homeostasis, regulation of biological effector molecules, gut microbiota analysis, sourcing of GRAS compliant complex carbohydrates and heme like molecules from microbial sources.