Science

baseclick is developing a diagnostic research tool for breast cancer, glioblastoma and prostate cancer. A very good candidate is the transcription XBP1. Expression of mutated XBP1 has been implicated in cancer progression. Its functions as transcription factor and depletion of normal XBP1 as well as expression of mutated XBP1 in cancer cells leads to cell division. Mutated XBP1 is produced in stressed cells and cancer situation when the IRE1 switches from its normal chaperon function in the ER to RNase function and unnatural cytoplasmic splicing of XBP1 mRNA occurs (XBP1s/XBP1u) leading to two forms of XBP1 protein in cancer cells. Triple-negative breast cancer (TNBC) lacks targeted therapies and has a worse prognosis than other breast cancer subtypes, underscoring an urgent need for new therapeutic targets and strategies. Our goal is to identify the best treatment for every single patient (enables personalized medicine) and monitor the treatment via transcriptome analysis.

National University of Ireland, Galway

The trans autophosphorylation of the kinase domain of IRE1 activates its unusual effector function, which causes the unconventional splicing of the mRNA that encodes a transcription factor XBP1. Abnormalities in XBP1 lead to ER stress and subsequently causes susceptibility for inflammatory processes that contribute to cancer. baseclick started a program whereby oligonucleotides are tested to inhibit RNase activity of IRE1 for anticancer therapy.

National University of Ireland, Galway

Development of RNA / DNA gene scissors for specific cleavage of viral SARS-CoV-2 genomes to inhibit viral replication. The overall goal is to design a SARS-CoV-2 drug based on an artificial gene editing method. Therefore, an oligo linked with a metal complexes capable of cutting will direct the “gene scissor” to the SARS-CoV-2 RNA in infected cells leading to inhibition of viral replication.

Dublin City University, Ireland

baseclick has begun a collaboration aimed at a fundamental understanding of the genetic and epigenetic mechanisms by which ribonucleic acids (RNAs) influence gene expression, development, epigenetic inheritance and evolution. The focus is on the regulation of epigenetic information by small RNAs (sRNAs). Our technology and experience in Next Generation Sequencing (NGS) opens up new dimensions in this research area. A collaboration was started to study small RNAs in order to understand the mechanisms of cellular and systemic gene regulation and virus defense.

Bergische Universität Wuppertal, Germany

Since 2014 baseclick is interested to utilizing click chemistry approaches to modify and conjugate targeting chemical entities to nucleic acids for tissue and cellular targeting and has filed several patents in this field even producing oligomeric modified nucleic acids for customer. One focus is directed to sugar conjugated nucleic acids, in particular RNA species such as siRNA, LNA or mRNA. These RNAs are conjugated to sugars such as glucose, mannose, GalNac and others for tissue and cellular targeting. In cooperation with various partners different sugar receptors are investigated. The modified nucleic acids are developed for targeted drug delivery strategies to treat infectious diseases, cancer and others.

University of Groningen, Netherlands