TOOL DEVELOPMENT

TOOL DEVELOPMENT

Antisense oligonucleotides (ASOs) have emerged as useful tools for knockdown of ncRNAs and hold great promise as therapeutics for the treatment of a wide range of human diseases. Most ASOs are chemically modified with phosphorothioate (PS) backbone linkages and different sugar modifications such as locked nucleic acids (LNAs) to enhance the binding affinity, stability and pharmacokinetic properties of ASOs. We have developed a tool for designing LNA-modified ASOs for ncRNA knockdown in cultured cells and in vivo. Our algorithm utilizes two ASO design paradigms with different mechanisms of action. ASOs promoting degradation of long noncoding RNA transcripts are designed as RNase H-recruiting LNA-modified PS gapmers with a central DNA gap flanked by LNA wings at the 5’ and 3’ end of the gapmer. ASOs for inhibiting miRNA function (antimiRs) are designed as LNA/DNA mixmers or short fully LNA-modified oligonucleotides with a complete PS backbone.
To address the growing need for computational approaches in RNA biology and biomedical research, we have developed a suite of bioinformatic tools. The following computational tools have been made available for researchers worldwide:
“ANGIOGENES” (http://angiogenes.uni-frankfurt.de) for expression profiles of transcripts in endothelial cells (Scientific Reports, 2016).
“C-It” (http://c-it.mpi-bn.mpg.de) for evolutionary-conserved, tissue-enriched, uncharacterized genes (Bioinformatics, 2010).
“C-It-Loci” (http://c-it-loci.uni-frankfurt.de) for evolutionary-conserved, tissue-enriched, protein-coding genes and lncRNAs (Bioinformatics, 2015).
“DRETools” (https://dretools.bitbucket.io) for studying differential RNA editings (F1000Research, 2018).
“Exon Array Analyzer (EAA)” (http://eaa.mpi-bn.mpg.de/) for analyzing Affymetrix GeneChip Exon 1.0 ST Arrays (Bioinformatics, 2009).
“FibroDB” (https://rnamedicine.shinyapps.io/FibroDB/) for expression profiles of transcripts in fibroblasts and during fibrosis (Non-Coding RNA, 2022).
“Gene Array Analyzer (GAA)” (http://gaa.mpi-bn.mpg.de/) for analyzing Affymetrix GeneChip Gene 1.0 ST Arrays (Nucleic Acids Research, 2012).
“noncoder” (http://noncoder.mpi-bn.mpg.de/) for quantifying the expression changes of lncRNAs and protein-coding genes from Affymetrix GeneChip Exon 1.0 ST Arrays (Nucleic Acids Research, 2013).
“RenalDB” (http://renaldb.uni-frankfurt.de) for in silico screening of enriched/specific transcripts of humans, mice, and zebrafish with respect to nephrotic tissues and cells, developmental stages, and other metadata (Briefings in Bioinformatics, 2018).
“RNAEditor” (http://rnaeditor.uni-frankfurt.de/) for analyzing RNA editing sites and islands from RNA-seq data (Briefings in Bioinformatics, 2017).
“SNP4Disease” (http://snp4disease.mpi-bn.mpg.de) for disease-related and/or -suspected SNPs.
“UGAHash” (http://ugahash.uni-frankfurt.de) for mapping human genomic features among various bioinformatics databases and versions of databases (Briefings in Bioinformatics, 2017).
“Vectools” (https://vectools.bitbucket.io) for working with vectors, matrices, and tables to perform statistics and machine learning analysis (F1000Research, 2018).