Viral Decay Acceleration™
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Koronis' Viral Decay Acceleration (VDA) technology evolved initially from the original work of Manfred Eigen, Nobel Laureate at the Max Planck Institute in Gottingen, Germany. He originated the concept of a “quasispecies” - the immensely large number of variants found in populations of virus, especially the RNA viruses (Scientific American July, 1993). A viral quasispecies is a highly structured and interrelated population of constantly evolving virus whose stability is defined by its genomic replication error rate. Intrinsic in this definition is the concept of a critical “error threshold” that sets the bounds for the allowed error rate and resultant diversity within the population and “error catastrophe”, the collapse of the population when that error rate is exceeded. The allowable extent of diversity of the viral population is further constrained by its environment. For example, the intact immune system and current drug therapy apply constant pressure to the allowable diversity. The adaptive, high natural rate of mutation allows the virus to rapidly develop drug resistance as a response to intense therapeutic drug-induced selective pressure.
In the case of HIV, the quasispecies results from the highly error-prone viral reverse transcriptase. Drs. Larry Loeb and Jim Mullins of the University of Washington and John Essigmann of the Massachusetts Institute of Technology, Koronis’ scientific founders, hypothesized that by presenting HIV with an error-inducing nucleoside triphosphate substrate, the viral genome mutation rate could be pushed beyond the allowable range of diversity thus extinguishing the population (Proceedings National Academy of Sciences. USA (1999) 96:1492-1497). This was demonstrated in cell culture using a nucleoside analog that normally base pairs with guanine but also frequently base pairs with adenine. This non-complementary base-pairing increased G to A and A to G mutations and ultimately, over the course of several viral replication cycles, resulted in viral ablation. This new approach to antiviral drug therapy, called Viral Decay Acceleration, is being applied to several human viral pathogens including HIV and HCV by Koronis Pharma.