Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation

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, aberr...

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Autores principales:	Prithi Raguraman, Akilandeswari Ashwini Balachandran, Suxiang Chen, Sarah D. Diermeier, Rakesh N. Veedu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antisense oligonucleotide splice switching cancer therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/475fc03a9e9d4f63b163ca53011b7bc0
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spelling	oai:doaj.org-article:475fc03a9e9d4f63b163ca53011b7bc02021-11-11T15:34:56ZAntisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation10.3390/cancers132155552072-6694https://doaj.org/article/475fc03a9e9d4f63b163ca53011b7bc02021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5555https://doaj.org/toc/2072-6694Splicing 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.Prithi RaguramanAkilandeswari Ashwini BalachandranSuxiang ChenSarah D. DiermeierRakesh N. VeeduMDPI AGarticleantisense oligonucleotidesplice switchingcancer therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5555, p 5555 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antisense oligonucleotide splice switching cancer therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	antisense oligonucleotide splice switching cancer therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Prithi Raguraman Akilandeswari Ashwini Balachandran Suxiang Chen Sarah D. Diermeier Rakesh N. Veedu Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation
description	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.
format	article
author	Prithi Raguraman Akilandeswari Ashwini Balachandran Suxiang Chen Sarah D. Diermeier Rakesh N. Veedu
author_facet	Prithi Raguraman Akilandeswari Ashwini Balachandran Suxiang Chen Sarah D. Diermeier Rakesh N. Veedu
author_sort	Prithi Raguraman
title	Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation
title_short	Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation
title_full	Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation
title_fullStr	Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation
title_full_unstemmed	Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation
title_sort	antisense oligonucleotide-mediated splice switching: potential therapeutic approach for cancer mitigation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/475fc03a9e9d4f63b163ca53011b7bc0
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Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation

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