RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription

RNA activation (RNAa) is a mechanism whereby RNA oligos complementary to genomic sequences around the promoter region of genes increase the transcription output of their target gene. Small activating RNA (saRNA) mediate RNAa through interaction with protein co-factors to facilitate RNA polymerase II...

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Autores principales:	Choon Ping Tan, Laura Sinigaglia, Valentí Gomez, Joanna Nicholls, Nagy A. Habib
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	small activating RNA saRNA oligonucleotide therapeutics RNA activation cancer treatment clinical trial Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/0f1f50fad12e4368b4b26d264f7522fe
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spelling	oai:doaj.org-article:0f1f50fad12e4368b4b26d264f7522fe2021-11-11T18:31:15ZRNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription10.3390/molecules262165301420-3049https://doaj.org/article/0f1f50fad12e4368b4b26d264f7522fe2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6530https://doaj.org/toc/1420-3049RNA activation (RNAa) is a mechanism whereby RNA oligos complementary to genomic sequences around the promoter region of genes increase the transcription output of their target gene. Small activating RNA (saRNA) mediate RNAa through interaction with protein co-factors to facilitate RNA polymerase II activity and nucleosome remodeling. As saRNA are small, versatile and safe, they represent a new class of therapeutics that can rescue the downregulation of critical genes in disease settings. This review highlights our current understanding of saRNA biology and describes various examples of how saRNA are successfully used to treat various oncological, neurological and monogenic diseases. MTL-CEBPA, a first-in-class compound that reverses CEBPA downregulation in oncogenic processes using CEBPA-51 saRNA has entered clinical trial for the treatment of hepatocellular carcinoma (HCC). Preclinical models demonstrate that MTL-CEBPA reverses the immunosuppressive effects of myeloid cells and allows for the synergistic enhancement of other anticancer drugs. Encouraging results led to the initiation of a clinical trial combining MTL-CEBPA with a PD-1 inhibitor for treatment of solid tumors.Choon Ping TanLaura SinigagliaValentí GomezJoanna NichollsNagy A. HabibMDPI AGarticlesmall activating RNAsaRNAoligonucleotide therapeuticsRNA activationcancer treatmentclinical trialOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6530, p 6530 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	small activating RNA saRNA oligonucleotide therapeutics RNA activation cancer treatment clinical trial Organic chemistry QD241-441
spellingShingle	small activating RNA saRNA oligonucleotide therapeutics RNA activation cancer treatment clinical trial Organic chemistry QD241-441 Choon Ping Tan Laura Sinigaglia Valentí Gomez Joanna Nicholls Nagy A. Habib RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription
description	RNA activation (RNAa) is a mechanism whereby RNA oligos complementary to genomic sequences around the promoter region of genes increase the transcription output of their target gene. Small activating RNA (saRNA) mediate RNAa through interaction with protein co-factors to facilitate RNA polymerase II activity and nucleosome remodeling. As saRNA are small, versatile and safe, they represent a new class of therapeutics that can rescue the downregulation of critical genes in disease settings. This review highlights our current understanding of saRNA biology and describes various examples of how saRNA are successfully used to treat various oncological, neurological and monogenic diseases. MTL-CEBPA, a first-in-class compound that reverses CEBPA downregulation in oncogenic processes using CEBPA-51 saRNA has entered clinical trial for the treatment of hepatocellular carcinoma (HCC). Preclinical models demonstrate that MTL-CEBPA reverses the immunosuppressive effects of myeloid cells and allows for the synergistic enhancement of other anticancer drugs. Encouraging results led to the initiation of a clinical trial combining MTL-CEBPA with a PD-1 inhibitor for treatment of solid tumors.
format	article
author	Choon Ping Tan Laura Sinigaglia Valentí Gomez Joanna Nicholls Nagy A. Habib
author_facet	Choon Ping Tan Laura Sinigaglia Valentí Gomez Joanna Nicholls Nagy A. Habib
author_sort	Choon Ping Tan
title	RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription
title_short	RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription
title_full	RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription
title_fullStr	RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription
title_full_unstemmed	RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription
title_sort	rna activation—a novel approach to therapeutically upregulate gene transcription
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0f1f50fad12e4368b4b26d264f7522fe
work_keys_str_mv	AT choonpingtan rnaactivationanovelapproachtotherapeuticallyupregulategenetranscription AT laurasinigaglia rnaactivationanovelapproachtotherapeuticallyupregulategenetranscription AT valentigomez rnaactivationanovelapproachtotherapeuticallyupregulategenetranscription AT joannanicholls rnaactivationanovelapproachtotherapeuticallyupregulategenetranscription AT nagyahabib rnaactivationanovelapproachtotherapeuticallyupregulategenetranscription
_version_	1718431805581819904

RNA Activation—A Novel Approach to Therapeutically Upregulate Gene Transcription

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