The past decade of genomics has revealed vast numbers of enigmatic non-protein coding RNAs - long noncoding RNAs (lncRNAs) – in our human genome. Many lncRNAs regulate pathogenic gene expression programmes, offering an opportunity for precise and safe therapies. Nevertheless, the vast space of lncRNAs remains largely unexplored and poorly understood. The intersection of cancer genomics, CRISPR-Cas genome-editing and antisense oligonucleotide (ASO) therapeutics now offers the means to identify, decipher and drug pathogenic lncRNAs across a range of diseases including cancer. In this talk, I will discuss our latest genomic discovery tools and resulting insights into the disease roles and molecular mechanisms of regulatory RNAs.