Title In silico Screening and Validation of Immunogenic Viral RNA Sequences
Authors Gökalp ÇELİK,Eda SÜER,Sadık ÇİĞDEM,Catherine Ann Moroski ERKUL,Burak YILMAZ,Yusuf ERKUL
Abstract Identification of RNA sequences found in the genomes of viruses that induce intracellular innate immunity has important implications in the fields of immunology and mRNA based gene therapy. Such findings help deepen our understanding of the innate immune system and can help us devise effective mRNA based gene therapies, i.e. mRNA replacements [1]. Although in vitro studies performed thus far have sporadically identified several immunogenic RNA sequences, it is still not possible to predict which sequences would be immunogenic within the cell. Within eukaryotic cellular and endosomal membranes, there are several receptors that are responsible for recognizing viral genomes. Some of these receptors recognize DNA with unmethylated CpG sequences (TLR9) or double stranded RNA (TLR3), while others such as TLR7, TLR8, PKR, or OAS are activated by single stranded (foreign) RNA molecules [2]. Crystal structure analysis of TLR8 revealed that this receptor can be activated by the binding of uridine and a short oligoribonucleotide with a predicted length of 2-20 bases [3]. Differential recognition of the viral genome by these receptors, which spares self RNAs, suggests the presence of selective activation by sequences that are frequently found in the viral genomes but that are either absent or infrequent in the human genome. We therefore identified 12 nucleotide-long RNA sequences within the genomes of RNA viruses and scored them according to their frequencies using a brute-force algorithm. For validation, we compared the scores of known immunogenic sequences to those of non-immunogenic sequences. Consequently, we note that in silico screening can be an effective method for identifying immunogenic RNA sequences. Following in vitro validation of identified immunogenic sequences, we aim to develop a codon optimization algorithm to design non-immunogenic mRNAs for gene replacement therapies.
Keywords Viral RNA, Immunogenicity, In silico screening, mRNA Vaccines, mRNA replacement
Journal BIBAD - Research Journal Of Biological Sciences
Issue Issue 2
Page 016-019
Year 2016
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