Research Groups

Mammalian Biology: Recombinant Gene Products

Research Interests and Description

Group Leader: Navin Khanna, MSc, PhD

Group Members

Research Interests

Genetically engineered biomolecules of medical use, subunit dengue vaccines, dengue reporter viruses, anti-dengue herbals, RNAi, codon-shuffling, pathogenesis of dengue and tuberculosis.

Description of Research

Genetically engineered biomolecules and viral diagnostics
The primary emphasis of our group’s research is the identification, design, development and transfer of technologies pertaining to laboratory scale production of recombinant proteins of medical use. The primary contribution is in the development of novel recombinant multiepitope proteins (MEPs), as inexpensive, highly sensitive and specific diagnostic intermediates for viral infections, like HCV, HIV and Dengue. The rapid HCV test developed, based on our designer protein has a CE certification and is being sold in several countries. In collaboration with the University of Turku, Finland, these designer proteins are being explored for developing unique 3-in-1 assays for the simultaneous detection of HIV, HCV and HBV infections, for use in blood bank settings.
Our laboratory-scale production strategy for Hepatitis B Vaccine has been successfully transferred to pharmaceutical companies in Iran and Egypt. In collaboration with the Helmholtz Institute of Infection Research, Germany, we have designed a simple and robust protocol, and together with the Biotechnology Development Group, ICGEB Trieste, enhanced production of human insulin. Recombinant dengue vaccine development
An ideal Dengue vaccine must be tetravalent, capable of protecting against all four DENVs. Currently tetravalent vaccines based on physical mixtures of four monovalent live attenuated viral vaccines are in clinical trials. The RGP group is working on an experimental sub-unit vaccine based on a discrete domain of the major DENV E protein.
Dengue virus inhibitors
We recently initiated a new programme to identify agents with anti-Dengue activity from indigenous herbal sources using an approach based on traditional Indian medicine (Ayurveda). This work has resulted in the identification of two herbal extracts capable of inhibiting the infectivity of all four DENV serotypes.  We are also screening a library of serine protease inhibitors, generated by a combinatorial chemistry approach, for molecules possessing DENV NS3 protease inhibitory activity.
Dengue Reporter Viruses
The PRNT assay, designed to measure the residual DENV infectivity in response to the presence of neutralizing antibodies or antiviral drugs, is labour-intensive, time-consuming and has very limited sample-handling capacity.  We are exploring the feasibility of creating green fluorescent protein (GFP)-expressing reporter DENVs in an attempt to set up rapid high throughput assays to replace the PRNT.
Synthesis and selection of de novo antibacterial proteins
We have realized the potential of the previously developed codon-shuffling method to create stand-alone de novo protein/peptide libraries, for their eventual use as antibacterial entities. Current efforts are directed towards creating similar antibacterial proteins against pathogenic organisms like Mycobacterium tuberculosis and in particular, focusing on some essential proteins from this pathogen, for example, the secretory proteins of M. tuberculosis. Further studies with such de novo peptides, like microarray analysis, may shed important light on their suitability as potential drug-like molecules against this and other pathogens.

Recent Publications

Khanam, S., Pilankatta, R., Khanna, N., Swaminathan, S. 2009. An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity. Vaccine 27, 6011-6021

Tiwari, A., Dutta, D., Khanna, N., Acharya, S. K., Sinha, S. 2009. Generation and characterization of high affinity humanized Fab against hepatitis B surface antigen. Mol. Biotechnol. 43, 29-40

Gurramkonda, C., Adnan, A., Gabel, T., Lunsdorf, H., Ross, A., Nemani, S.K., Swaminathan, S., Khanna, N., Rinas, U. 2009. Simple high-cell density fed-batch technique for high-level recombinant protein production with Pichia pastoris: Application to intracellular production of Hepatitis B surface antigen. Microb. Cell Fact. 8, 13

Swaminathan, S., Khanna, N. 2009. Dengue: Recent advances in biology and current status of translational research. Curr Mol Med. 9, 152-173

Tiwari, A., Khanna, N., Acharya, S.K., Sinha, S. 2009. Humanization of high affinity anti-HBs antibody by using human consensus sequence and modification of selected minimal positional template and packing residues. Vaccine 27, 2356-2366

Patents

Batra, G., Hapugoda, M., Chaudhry, S., Swaminathan, S., Khanna, N. Tetravalent dengue specific domain III based chimeric recombinant protein. PCT/IN06/00316

Khanna, N. and Swaminathan, S. A novel dengue envelope domain III-based tetravalent protein vaccine. 1259/DEL/2007