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Published (Version of Record)CC BY V4.0, Open Access
Journal article
Antisense oligonucleotide-mediated splice switching: Potential therapeutic approach for cancer mitigation
Cancers, Vol.13(21), Article 5555
2021
Abstract
Splicing is an essential process wherein precursor messenger RNA (pre-mRNA) is reshaped into mature mRNA. In alternative splicing, exons of any pre-mRNA get rearranged to form mRNA variants and subsequently protein isoforms, which are distinct both by structure and function. On the other hand, aberrant splicing is the cause of many disorders, including cancer. In the past few decades, developments in the understanding of the underlying biological basis for cancer progression and therapeutic resistance have identified many oncogenes as well as carcinogenic splice variants of essential genes. These transcripts are involved in various cellular processes, such as apoptosis, cell signaling and proliferation. Strategies to inhibit these carcinogenic isoforms at the mRNA level are promising. Antisense oligonucleotides (AOs) have been developed to inhibit the production of alternatively spliced carcinogenic isoforms through splice modulation or mRNA degradation. AOs can also be used to induce splice switching, where the expression of an oncogenic protein can be inhibited by the induction of a premature stop codon. In general, AOs are modified chemically to increase their stability and binding affinity. One of the major concerns with AOs is efficient delivery. Strategies for the delivery of AOs are constantly being evolved to facilitate the entry of AOs into cells. In this review, the different chemical modifications employed and delivery strategies applied are discussed. In addition to that various AOs in clinical trials and their efficacy are discussed herein with a focus on six distinct studies that use AO-mediated exon skipping as a therapeutic strategy to combat cancer.
Details
- Title
- Antisense oligonucleotide-mediated splice switching: Potential therapeutic approach for cancer mitigation
- Authors/Creators
- P. Raguraman (Author/Creator) - Murdoch UniversityA.A. Balachandran (Author/Creator) - Murdoch UniversityS. Chen (Author/Creator) - Murdoch UniversityS.D. Diermeier (Author/Creator) - University of OtagoR.N. Veedu (Author/Creator) - Murdoch University
- Publication Details
- Cancers, Vol.13(21), Article 5555
- Publisher
- MDPI
- Identifiers
- 991005540077607891
- Copyright
- © 2021 by the authors
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.170 Nucleic Acids Chemistry
- 2.170.988 Oligonucleotide Modifications
- Web Of Science research areas
- Oncology
- ESI research areas
- Clinical Medicine