Research Groups

Mammalian Biology: Recombinant Gene Products

Group Leader

Research Interests and Description
Group Members

Navin Khanna

International Centre for Genetic Engineering and Biotechnology
Aruna Asaf Ali Marg
110 067 New Delhi, India

E-mail: navin@icgeb.res.in
Office tel: +91-11-26742357/60, 26741358, 2741361
Office fax: +91-11-26742316

Education

University of Lucknow, Department of Biochemistry, Lucknow, India, MSc, 1977
All India Institute of Medical Sciences, Department of Biochemistry, New Delhi, India, PhD, 1983

Career History

Since 1994, Group Leader, Recombinant Gene Products Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
1990-1994, Senior Research Scientist, ICGEB, New Delhi.
1989-1990, Research Assistant Professor, Department of Biochemistry and Molecular Biology, University of California, Irvine, USA.
1989-1987, Postgraduate Research Biologist, Centre for Molecular Genetics, University of California, San Diego, USA.
1987-1983, Alberta Heritage Foundation Fellow at Cell Regulation Group, University of Calgary, Alberta, Canada.

Teaching Activity

Tutoring in the ICGEB Ph.D. Programme.

Scientific Activity

Current research focuses on genetically engineered biomolecules of medical use. Primary contribution is in the development of novel recombinant designer proteins as inexpensive, highly sensitive and specific diagnostic intermediates for viral infections, like HCV, HIV and Dengue virus. Diagnostic kits based on these proteins have been commercialized. The rapid HCV test developed, based on our designer protein, has a CE certification and is being sold in several countries. The availability of these designer proteins and high affinity Hepatitis B virus monoclonal antibodies has reduced the production cost of these diagnostic kits for detection of HCV and HBV infections.  In collaboration with Professor Kim Pettersson at the University of Turku, Finland, these designer proteins are being explored for developing novel reporter assays using Terbium-labelled nanoparticles. This collaboration is aiming to develop a unique 3-in-1 assay for the simultaneous detection of HIV, HCV and HBV infections, for use in blood bank settings. With Finnish collaboration, efforts are also being made to identify additional Dengue virus specific epitopes using their proprietary epitope phage display library.

Earlier, we had developed a high copy Pichia clone for the laboratory scale production of HBsAg. This “know-how” has been successfully transferred to pharmaceutical companies in Iran and Egypt. Recently, in collaboration with Professor Ursula Rinas at Helmholtz Institute of Infection Research, we have designed a simple two-phase high-cell density fed batch procedure composed of a glycerol batch and a constant methanol fed-batch phase based on robust FID online analytics which is proposed to generate ~7 times more HBsAg than previously reported using Pichia based expression systems. Using this robust feeding protocol, maximum concentrations of ~7 grams HBsAg per liter culture broth were obtained. The amount of soluble HBsAg, competent for assembly into characteristic virus-like particles (VLPs), an attribute critical to its immunogenicity and efficacy as a hepatitis B vaccine, reached 2.3 grams per liter of culture broth. These research findings have been extended to a tri-party collaboration with the Technology transfer group at ICGEB Trieste, and the German group, for the enhance production of human insulin. Currently, our efforts have resulted in the secretion of 3 gram of insulin precursor from recombinant Pichia pastoris.

Other research interests include anti dengue and anti HCV compounds from natural sources and development of experimental Dengue tetravalent subunit vaccine in yeast

Selected 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. DOI: 10.1016/j.vaccine.2009.07.073 In press

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. DOI: 10.1007/s12033-009-9165-9 In press

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

Chawla, T., Khanna, N., Swaminathan, S. Adenovirus vectored vaccines. 2008. Expert Opin. Therap. Patents 18, 1-15

Etemad, B., Batra, G., Raut, R., Dahiya, S., Khanam, S., Swaminathan, S., Khanna, N. 2008. An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes. Am J Trop Med Hyg. 79, 353-363

Swaminathan, S., Khanna, N. 2008. Commentary: Wake up call for dengue. Nature India

Khanam, S., Rajendra, P., Khanna, N., Swaminathan, S. 2007. An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes. BMC Biotechnol. 7, 10

Rao, A., Ram, G., Saini, A. K., Vohra, R., Kumar, K., Singh, Y., Ranganathan A. 2007. Synthesis and selection of de novo proteins that bind and impede cellular functions of an essential mycobacterial protein. Appl Environ Microbiol. 73, 1320-1331

AnandaRao, R., Swaminathan, S., Fernando, S., Jana, A.M., Khanna, N. 2006. Recombinant multiepitope protein for the early detection of dengue infections. Clin Vaccine Immunol. 13, 59-67

Bose, B., Khanna, N., Acharya, S.K., Sinha, S. 2006. Generation and characterization of a single- gene mouse-human chimeric antibody against Hepatitis B surface antigen. J Gastroenterol Hepatol. 21, 1439-1447

Bose, B., Khanna, N., Acharya, S.K., Sinha, S. 2006. Generation and characterization of a high affinity chimaeric antibody against Hepatitis B surface antigen. Biotechnol Appl Biochem. 43, 93-101

Chaudhry, S., Swaminathan, S., Khanna, N. 2006. The murine charged multivesicular body protein 2A, CHMP2A interacts with the 5’and 3’ terminal regions of dengue virus complementary minus-strand RNA. Am J Infect Dis. 2, 18-27

Chugh, D.A., Jain, S.K., Khanna. N. 2006. A novel recombinant multiepitope protein as a hepatitis C diagnostic intermediate of high sensitivity and specificity. Protein Expr Purif. 47, 319-328

Gopalan, G., Chopra, S., Ranganathan, A., Swaminathan, K. 2006. Crystal structure of uncleaved L-aspartate-alpha -decarboxylase from Mycobacterium tuberculosis. Proteins 65, 796-802

Khanam, S., Etemad, B., Khanna, N. Swaminathan, S. 2006. Induction of neutralizing antibodies specific to dengue virus serotypes 2 and 4 by a bivalent antigen composed of linked envelope domains III of these two serotypes. Am J Trop Med Hyg. 74, 266-277

Khanam, S., Khanna, N., Swaminathan, S. 2006. Induction of antibodies and T cell responses by dengue virus type 2 envelope domain III encoded by plasmid and adenoviral vectors. Vaccine 24, 6513-6525

Kolli, R., Khanam, S., Jain, M. Ganju, L., Sai Ram, M., Khanna, N., Swaminathan, S. 2006. A synthetic dengue virus antigen elicits enhanced antibody titers when linked to, but not mixed with, Mycobacterium tuberculosis HSP70 domain II. Vaccine 24, 4716-4726

Shenoy, S.R., Shiva Kameshwari, M.N., Swaminathan, S., Gupta, M.N. 2006. Major antifungal activity from the bulbs of Indian squill Urginea indica is a chitinase. Biotechnol Prog. 22, 631-637

Patents

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

Katiyar, C. K., Khanna, N., Upadhyay, D. J., Swaminathan, S., Srinivas, K., Sharma, N., Kanaujia, A., Sood, R., Singhal, S., Shukla, G., Duggar, R., Pareek, P.K., Singh, Y., Khan, S., Raut, R. 2009. Anti dengue activity of Cissampelos pariera extracts (Patent application # 141/DEL/2009)

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

Tiwari, A., Sinha, S., Khanna, N., Acharya, S. K. 2008. A humanized high affinity recombinant antibody against hepatitis B surface antigen (Patent application # 190/DEL/2008)