csbpaper - A Pattern Matching Algorithm for Codon...

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A Pattern Matching Algorithm for Codon Optimization and CpG Motif- Engineering in DNA Expression Vectors Ravi Vijaya Satya and Amar Mukherjee School of Engineering and Computer Science University of Central Florida Orlando, FL 32816 rvijaya, [email protected] Udaykumar Ranga Jawaharlal Nehru Center for Advanced Scientific Research Jakkur, Bangalore, India [email protected] Abstract Codon optimization enhances the efficiency of DNA expression vectors used in DNA vaccination and gene therapy by increasing protein expression. Additionally, certain nucleotide motifs have experimentally been shown to be immuno-stimulatory while certain others immuno- suppressive. In this paper, we present algorithms to locate a given set of immuno-modulatory motifs in the DNA expression vectors corresponding to a given amino acid sequence and maximize or minimize the number and the context of the immuno-modulatory motifs in the DNA expression vectors. The main contribution is to use multiple pattern matching algorithms to synthesize a DNA sequence for a given amino acid sequence and a graph theoretic approach for finding the longest weighted path in a directed graph that will maximize or minimize certain motifs. This is achieved using O(n 2 ) time, where n is the length of the amino acid sequence. Based on this, we develop a software tool. Key Words: Codon optimization, immuno-modulatory motifs, multiple pattern matching, longest weighted path. 1. Introduction DNA vaccines have revolutionized the field of vaccine technology by demonstrating the ability to induce humoral and cellular immune responses in experimental animals and humans [9]. Immunization of animals with plasmid DNA encoding a protein antigen was an accidental observation that eventually led the way to a novel strategy of immunization. DNA vaccines, also known as "naked DNA" or "nucleic acid" vaccines, encode the antigens of pathogenic organisms including viruses, bacteria, fungi and parasites [40]. The protein antigen is processed within the cell and presented by the MHC-I and –II pathways thereby eliciting specific immune responses essential for controlling pathogenic infections [2]. Although DNA vaccines have been successful in generating strong immune responses in smaller animal model such as mouse, they have not been as efficient in larger species such as primates and humans [23, 3, 25, 4]. Stimulating both the arms of the immune system is often desirable for efficient control of infectious diseases especially in the larger animals. In the case of recombinant protein vaccines, immune-enhancers technically known as adjuvants, such as Freund’s adjuvants and Alum, are in use to enhance antigen specific immune responses. However, no such adjuvants are available for use in the context of DNA vaccines. The lack of suitable adjuvants for DNA vaccines is one important reason for the poor performance of the DNA vaccines in larger animals.
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