Therapeutic applications of trans-splicing

• Published in: British medical bulletin Vol. 136; no. 1; pp. 4 - 20
• Main Authors: Hong, Elizabeth M, Ingemarsdotter, Carin K, Lever, Andrew M L
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15-12-2020
• Subjects: Editor's Choice; Humans; Inteins; Invited Review; Proteins; Trans-Splicing; split intein-mediated trans-splicing; ribozyme-mediated trans-splicing; infectious disease; spliceosome-mediated RNA trans-splicing (SMaRT); gene therapy; trans-splicing; cancer; genetic disease
• ISSN: 0007-1420; 1471-8391
• DOI: 10.1093/bmb/ldaa028

RNA trans-splicing joins exons from different pre-mRNA transcripts to generate a chimeric product. Trans-splicing can also occur at the protein level, with split inteins mediating the ligation of separate gene products to generate a mature protein.
Comprehensive literature search of published research papers and reviews using Pubmed.
Trans-splicing techniques have been used to target a wide range of diseases in both in vitro and in vivo models, resulting in RNA, protein and functional correction.
Off-target effects can lead to therapeutically undesirable consequences. In vivo efficacy is typically low, and delivery issues remain a challenge.
Trans-splicing provides a promising avenue for developing novel therapeutic approaches. However, much more research needs to be done before developing towards preclinical studies.
Increasing trans-splicing efficacy and specificity by rational design, screening and competitive inhibition of endogenous cis-splicing.