Genome-wide studies revealed that only 1-2% of the human genome encodes for proteins, while most of the genome can be transcribed. Of these "non-coding" transcripts, long non-coding RNAs (lncRNAs) represent the largest and most diverse class. LncRNAs have been implicated as oncogenes or tumour suppressors in a number of cancer types.
The two main challenges the field is currently facing are identifying (1) the most clinically actionable lncRNAs, and (2) the best approach to drug lncRNAs.
To address #1, we developed AURORA, a robust and versatile target ID and validation platform by combining bioinformatic analyses, CRISPR screening, and preclinical models including organoids and mouse models. We exemplified our pipeline in several types of cancer and demonstrated the design and development of lncRNA-targeting antisense oligonucleotides (ASOs) with drug-like properties.
Our results suggest that we are able to identify lncRNAs that act as important drivers of tumor progression and have developed specific and potent ASO drugs.