Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/35208
Title: HOST RESPONSES TO RECOMBINANT BACULOVIRAL VECTORS IN ANIMAL MODELS
Authors: GHAYATHRI BALASUNDARAM
Keywords: baculovirus, gene therapy, host immune response, serum-resistance, virus purification, non-human primates
Issue Date: 20-Jan-2012
Source: GHAYATHRI BALASUNDARAM (2012-01-20). HOST RESPONSES TO RECOMBINANT BACULOVIRAL VECTORS IN ANIMAL MODELS. ScholarBank@NUS Repository.
Abstract: Recombinant insect baculoviruses (rBV) have been emerging as promising gene delivery vectors. Though mammalian host responses to baculoviral transduction is not yet completely known, there have been reports of rBV eliciting immune responses and getting inactivated by serum complement system, thus questioning their suitability for clinical trials. This study aims to assess the host responses to baculoviral transduction, particularly in the brain and develop methods to attenuate them. To substantially reduce unwanted immune responses due to contaminants in rBV formulations, a membrane chromatography based purification method was developed and tested for suitability in mice brains. Host responses to purified rBV was assessed in non human primates - cynomolgus monkeys that share very high genomic similarity with humans by analyzing the global gene expression profiles using cDNA microarray technology upon acute central administration. It was observed that rBV inoculation caused no major abnormalities to the animals but induced anti-viral, primarily, innate immune responses and complement protein activation as major reactions. To overcome the inactivation by serum complement proteins, a novel method of coating rBV with cationic lipids was developed and tested in vitro. These findings will serve as a guide to rational therapeutic applications of baculoviral vectors.
URI: http://scholarbank.nus.edu.sg/handle/10635/35208
Appears in Collections:Ph.D Theses (Open)

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