Long non-coding RNA-targeting therapeutics: discovery and development update.

Introduction: lncRNAs are major players in regulatory networks orchestrating multiple cellular functions, such as 3D chromosomal interactions, epigenetic modifications, gene expression and others. Due to progress in the development of nucleic acid-based therapeutics, lncRNAs potentially represent easily accessible therapeutic targets.

Areas Covered: Currently, significant efforts are directed at studies that can tap the enormous therapeutic potential of lncRNAs.

Amplifying gene expression with RNA-targeted therapeutics.

Many diseases are caused by insufficient expression of mutated genes and would benefit from increased expression of the corresponding protein. However, in drug development, it has been historically easier to develop drugs with inhibitory or antagonistic effects. Protein replacement and gene therapy can achieve the goal of increased protein expression but have limitations.

Natural antisense transcripts as drug targets.

The recent discovery of vast non-coding RNA-based regulatory networks that can be easily modulated by nucleic acid-based drugs has opened numerous new therapeutic possibilities. Long non-coding RNA, and natural antisense transcripts (NATs) in particular, play a significant role in networks that involve a wide variety of disease-relevant biological mechanisms such as transcription, splicing, translation, mRNA degradation and others. Currently, significant efforts are dedicated to harnessing these newly emerging NAT-mediated biological mechanisms for therapeutic purposes.