Research Groups

Mammalian Biology: Recombinant Gene Products

Research Interests and Description

Group Leader: Navin Khanna, 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
Current research focuses on genetically engineered biomolecules of medical use. A primary contribution is in the development of novel recombinant designer proteins as inexpensive, highly sensitive and specific diagnostic intermediates for viral infections, such as HCV, HIV and Dengue virus. The availability of high quality diagnostic intermediates for HCV, HIV and HBV from our laboratory to manufacturers of diagnostic kits has reduced production costs significantly. These kits are being manufactured in India and are being used in several Asian and African countries.
In collaboration with Prof. Kim Pettersson, University of Turku, Finland, these designer proteins are being explored for developing novel reporter assays using Terbium-labelled nanoparticles. Work is underway to create a unique 3-in-1 assay for the simultaneous detection of HIV, HBV and HCV infections, for use in blood bank settings. Based on our diagnostic intermediates, a test has been commercialized for the detection of dengue NS1 antigen from all 4 dengue serotypes. This kit has been launched in 2010 and has been a great success on the Indian market.
In collaboration with Prof. Ursula Rinas, Helmholtz Institute of Infection Research, Germany, we have used our HBsAg clone to design a robust high cell density protocol capable of yields as high as ~7 g/L culture broth. Recently, our lab-scale technology to produce HBsAg in the yeast has been transferred to a company in China. This high cell density cultivation process, extended to a tri-party collaboration with ICGEB Trieste, has resulted in the secretion of insulin precursor to 3g/L culture broth, and this newly developed know-how for high-level secretion of rh-Insulin has been transferred to China.
Recombinant dengue vaccine development
Four serotypes of Dengue viruses (DENV-1, -2, -3 and -4) cause Dengue disease, for which there is currently no vaccine or antiviral drug. The RGP Group is interested in developing sub-unit vaccines, based on DENV envelope domain III, which mediates virus entry into cells and elicits virus-neutralizing antibodies. At present, our research activities are focused towards the development of experimental Dengue tetravalent subunit vaccine in yeast. In consultation with the Indo-US Vaccine Action Program, we have created DENV-2 EDIII HBsAg virus-like particles (VLPs) and are currently evaluating these physically and functionally.
Dengue Reporter Viruses
We have established collaboration with the University of Helsinki, Finland to develop recombinant dengue viruses encoding a reporter gene with the aim of establishing high throughput viral infectivity assays to aid our dengue vaccine development work.
Synthesis and selection of de novo antibacterial proteins
Current efforts are directed towards extending the previously developed codon-shuffling method to create antibacterial proteins against pathogenic organisms, such as Mycobacterium tuberculosis, focussing on some essential proteins from this pathogen. During our efforts to isolate potential binding partners of key secretory proteins of M. tuberculosis from a human lung protein library, we isolated peptides that strongly bound the virulence determinant protein Esat6. We have also initiated studies towards finding potent binders and inhibitors of some selected proteins of DENV-2.

Recent Publications

Batra, G., Nemani, S.K. Tyagi, P., Swaminathan, S., Khanna, N. 2011. Evaluation of envelope domain III-based single chimeric tetravalent antigen and monovalent antigen mixtures for the detection of anti-dengue antibodies in human sera. BMC Infect Dis 11, 64 PubMed link

Gurramkonda, C., Polez, S., Skoko, N., Adnan, A., Gäbel, T., Chugh, D., Swaminathan, S., Khanna, N., Tisminetzky, S., Rinas, U. 2010. Application of simple fed-batch technique to high-level secretory production of insulin precursor using Pichia pastoris with subsequent purification and conversion to human insulin. Mircob Cell Fact 9, 31 PubMed link

Myyryläinen, T., Talha, S. M., Swaminathan, S., Vainionpää, R., Soukka, T., Khanna, N., Pettersson, K. 2010. Simultaneous detection of human immunodeficiency virus 1 and hepatitis B virus infections using a dual-label time-resolved fluorometric assay. J Nanobiotechology 8, 27 PubMed link

Pilankatta, R., Chawla, T., Khanna, N., Swaminathan, S. 2010. The prevalence of antibodies to adenovirus serotype 5 in adult Indian population and implications for adenovirus vector vaccines. J Med Virol 82, 407-414 PubMed link

Swaminathan, S., Batra, G., Khanna, N. 2010. Dengue vaccines: state of the art. Expert Opin Therap Pat 20, 819-835 PubMed link

Talha, S.M., Salminen, T., Chugh, D.A., Swaminathan, S., Soukka, T., Pettersson, K., Khanna, N. 2010. Inexpensive designer antigen for anti-HIV antibody detection with high sensitivity and specificity. Clin Vac Immunol 17, 335-341 PubMed link