siRNA-BASED THERAPEUTICS & INFECTIOUS DISEASES

RNA interference (RNAi) is an evolutionarily conserved biological mechanism adopted by many organisms to effectively control gene expression. The exquisite specificity and robustness of RNAi have generated an immense interest in using RNAi as research tools to address fundamental biological processes. Numerous studies have provided the proof of concept that diseases can be targeted by therapeutic RNAi against a wide range of human disorders, including cancer, infectious diseases and metabolic disorders. Additionally, there is a growing interest in using RNAi for pest control as a traditionally applied insecticide and within genetically modified plants.

RNAi-based therapy offer several advantages over current therapeutic approaches using small molecules, monoclonal antibodies and proteins. Unlike traditional drugs, RNAi-based therapeutics with high selectivity and potency can be easily synthesized and optimized against all classes of gene targets.

RNA interference (RNAi) is an evolutionarily conserved biological mechanism adopted by many organisms to effectively control gene expression. The exquisite specificity and robustness of RNAi have generated an immense interest in using RNAi as research tools to address fundamental biological processes. Numerous studies have provided the proof of concept that diseases can be targeted by therapeutic RNAi against a wide range of human disorders, including cancer, infectious diseases and metabolic disorders. Additionally, there is a growing interest in using RNAi for pest control as a traditionally applied insecticide and within genetically modified plants.

RNAi-based therapy offer several advantages over current therapeutic approaches using small molecules, monoclonal antibodies and proteins. Unlike traditional drugs, RNAi-based therapeutics with high selectivity and potency can be easily synthesized and optimized against all classes of gene targets.

The future of RNAi researches is exciting and there are many applications to be considered in this field. There is great hope that in the near future RNAi based treatment for diseases such as Huntington’s disease, HIV, cancer and other genetic based or infectious diseases will be available. As with any new therapeutic paradigm, several issues need to be addressed in order to translate and leverage the value of RNAi technology from the laboratory into the clinic.

As part of the Quark Pharmaceuticals – Biocon collaboration, the power of siRNA will be leveraged to develop novel therapeutics and progress them to proof of concept studies.

The key areas of focus are:

  • Build a technology platform to develop novel siRNA based therapeutics against a range of human diseases
  • Institute a molecular surveillance framework to track hospital acquired infections
  • Understand and map the emergence and evolution of bacterial drug resistance
  • Build a translational approach to identify biomarkers of disease progression and response to treatment with biological agents

People

 Dr Vasan Sambandamurthy

Dr Vasan Sambandamurthy

Publications (Recent)

  • Ramachandran S,…., Sambandamurthy VK# 2014. N-Aryl-2-aminobenzimidazoles: Novel, Efficacious, Antimalarial Lead Compounds. J Medicinal Chemistry; Jul 21. (Corresponding Author)
  • Hameed S, …., Sambandamurthy VK# 2014. Aminoazabenzimidazoles, a novel class of orally active antimalarial agents. J Medicinal Chemistry; 57(13):5702-13 (Corresponding Author)
  • Balasubramanian V,.., Sambandamurthy VK#, 2014. Bactericidal activity and mechanism of action of AZD5847, a novel oxazolidinone for treatment of tuberculosis. Antimicro Agents & Chemother; 58(1):495-502. (Corresponding Author)
  • Shirude PS,.., Sambandamurthy VK, 2013. Aminopyrazinamides: novel and specific GyrB inhibitors that kill replicating and nonreplicating Mycobacterium tuberculosis. ACS Chemical Biology; 8(3):519-23.
  • Schmitt EK, Riwanto M, Sambandamurthy VK, et al., 2011. The natural product cyclomarin kills Mycobacterium tuberculosis by targeting the ClpC1 subunit of the caseinolytic protease. Angew Chem Int Ed Engl.; 50(26):5889-91.
  • Kurabachew M,…, Sambandamurthy VK, 2008. Lipiarmycin targets RNA polymerase & has good activity against multidrug-resistant strains of Mycobacterium tuberculosis. J Antimicrob Chemother. 62(4):713-9 (Corresponding Author)
  • Sambandamurthy VK*, Derrick SC*, et al., 2006. Mycobacterium tuberculosis DeltaRD1 DeltapanCD: a safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis. Vaccine; 24(37-39): 6309-20. (equal contributions)
  • Hingley-Wilson S, Sambandamurthy VK & Jacobs Jr. WR, 2003. Survival perspectives from the world’s most successful pathogen, Mycobacterium tuberculosis. Nature Immunology; 4: 949-957.
  • Sambandamurthy VK,…, Jacobs WR, 2002. A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis.Nature Medicine; 8: 1171-4.