Bioinformatics
At exRNA Therapeutics, the journey of developing therapies is a collaborative effort, with bioinformatics playing a crucial role in deciphering complex biological data. The team performs whole genome sequencing to understand the genetic blueprint of new drugs, analyzes interactions between drug sequences and human mRNAs to uncover mechanisms of action, and identifies target mRNAs for precise disease targeting. The department of bioinformatics also explores cross-species interactions to gauge the broader applicability of our drugs against various pathogens, such as ESKAPE bacteria and HIV. We develop advanced bioinformatics tools, like specialized search engines, to streamline research processes and provide quick insights into drug interactions. Additionally, we manage custom gene and disease-specific databases, which serve as essential resources for ongoing research and development. Our work exemplifies the significant impact of bioinformatics in modern drug development, driving forward our mission to combat challenging diseases through the synergy of advanced data analysis and innovative tool creation.
Projects
Target Prediction of G1
RNA-RNA interaction analysis of G1 was carried out using IntaRNA3, a computational tool designed for predicting RNA-RNA interactions, particularly focusing on the interaction between small non-coding RNAs (sRNAs) and their target mRNAs. This analysis led us to identification of mRNAs which are being downregulated by our ASO.
RNA secondary structure prediction for target site identification
RNA secondary structure of all the G1 targeted mRNAs were carried out using RNAfold to identify the target site where the ASO binds with the mRNA. The analysis resulted in ASO binding with the mRNAs at the loop(hairpin) position increasing the ASO binding efficiency or much better antisense activity.
G1 Target Database for Rare and Orphan Diseases
The Department of Bioinformatics, exRNA Therapeutics created a database which comprises all the Rare and Orphan disease targeted or which are being downregulated by G1. This ASO specific database allows the researchers at exRNA Therapeutics to browse through and search for related information at a single place.
Developing a G1 Drug-mRNA Interaction Search Engine
Our team at exRNA Therapeutics, developed a specific search engine which allows our researchers to access all the information related to the mRNAs in relation to G1 at the click of a button.
Mutation-specific antisense therapy design
Mutation specific analysis of the mRNAs were done to identify the points where the mRNAs are mutated and if G1 is targeting those mutated sites. This led us to develop mutation specific therapy design.
BLAST Analysis: NCBI’s nucleotide BLAST was used to compare the mRNA sequence against the human genome database to identify any mutations.
Mutation Identification: Analysis of the BLAST results was done to pinpoint mutations in the mRNA sequence, particularly at the binding sites.
Binding Affinity Assessment: Evaluation of the results were done to check whether these mutations increase or decrease the binding affinity of the drug or antisense molecule to the mRNA.
Functional Implication: Assessment led us to identification of Mutation-specific antisense therapy design as mutations lead to several rare diseases and targeting those sites with our ASO has shown significantly good results.