long non-coding RNA

Long non-coding RNAs (lncRNAs) are >200 nucleotide long RNA molecules that do not code for proteins. According to the latest version of LNCipedia, at least 3 times more human lncRNA genes have been identified compared to protein coding mRNAs, and this numbers continues to grow. LncRNAs function through a myriad of mechanisms and have various important roles, most of which involve regulation of gene expression. As such, lncRNAs are crucial for normal development and involved in human diseases, including cancer.

lncRNAs in cancer

Increasing evidence suggests an important role for lncRNA deregulation in cancer development and progression. Prominent examples include the recently discovered lncRNAs HOTAIR, MALAT1, NEAT1 and SAMMSON. Unlike mRNAs, lncRNAs have remarkable cell type-specific expression, making them excellent candidates for developing safe selective treatments with minimal side effects.

RNA-targeting therapies

Developing drugs against protein targets has proven to be an inefficient process. The USA FDA-approved small-molecule drugs currently on the market target only 285 proteins. In contrast, any RNA molecule in the transcriptome can in principle be therapeutically inhibited using nucleic acid-based drugs, using for instance antisense or RNA interference technology. The newest generation of such nucleic acid-based drugs are self-delivering, obviating the need for a delivery vehicle to cross cell membranes in the body and bypassing a major challenge in targeted drug development. Once inside the cell, these drugs typically display high target-specificity, being able to distinguish a single nucleotide mismatch. Compared to small molecules, rational drug development using nucleic acid-based drugs has a much faster development track.

Biogazelle’s platform

Biogazelle has proprietary data and knowledge to prioritize candidate therapeutic RNA targets in liver, colon and lung cancer. Thousands of nucleic-acid based compounds directed against hundreds of lncRNA targets are currently being evaluated in large-scale in vitro screenings, followed by pre-clinical animal model studies. Biogazelle has experience with various antisense and RNAi technologies (including cEt-, MOE-, 2’O-Me- and LNA-modified antisense oligonucleotides and sd-rxRNAs) to modulate RNA expression.