Development of a Tethered mRNA Amplifier to increase protein expression

Bahareh Torkzaban; Ryan Kawalerski; Jeff Coller

doi:10.1002/biot.202200214

Development of a Tethered mRNA Amplifier to increase protein expression

Bahareh Torkzaban, Ryan Kawalerski, Jeff Coller

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Herein, we present a novel method to specifically increase a messenger RNA's (mRNA) expression at the post-transcriptional level. This is accomplished using what we term a “Tethered mRNA Amplifier.” The Tethered mRNA Amplifier specifically binds an mRNA's 3′ untranslated region and enhances its stability/translation, often doubling protein output. We test this approach on several transcripts associated with haploinsufficiency disorders and increase their steady-state expression in cell culture. We suggest this approach may be a tenable therapeutic modality with precise activity and broad-spectrum application.

Original language	English (US)
Article number	2200214
Journal	Biotechnology Journal
Volume	17
Issue number	10
DOIs	https://doi.org/10.1002/biot.202200214
State	Published - Oct 2022

Keywords

gene expression
haploinsufficiency
mRNA metabolism
mRNA therapeutics
mRNA translation

ASJC Scopus subject areas

Applied Microbiology and Biotechnology
Molecular Medicine

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10.1002/biot.202200214

Cite this

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abstract = "Herein, we present a novel method to specifically increase a messenger RNA's (mRNA) expression at the post-transcriptional level. This is accomplished using what we term a “Tethered mRNA Amplifier.” The Tethered mRNA Amplifier specifically binds an mRNA's 3′ untranslated region and enhances its stability/translation, often doubling protein output. We test this approach on several transcripts associated with haploinsufficiency disorders and increase their steady-state expression in cell culture. We suggest this approach may be a tenable therapeutic modality with precise activity and broad-spectrum application.",

keywords = "gene expression, haploinsufficiency, mRNA metabolism, mRNA therapeutics, mRNA translation",

author = "Bahareh Torkzaban and Ryan Kawalerski and Jeff Coller",

note = "Funding Information: The authors thank Drs. Harvey Lodish, Gopi Shanker, Peter Eimon, and the members of the Coller Lab for helpful discussions. Funding is provided by a grant to J.C. from Tevard Biosciences. R.K.: Data curation; writing – review & editing. J.C.: Conceptualization; formal analysis; funding acquisition; project administration; supervision; writing – original draft. Publisher Copyright: {\textcopyright} 2022 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.",

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AU - Coller, Jeff

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N2 - Herein, we present a novel method to specifically increase a messenger RNA's (mRNA) expression at the post-transcriptional level. This is accomplished using what we term a “Tethered mRNA Amplifier.” The Tethered mRNA Amplifier specifically binds an mRNA's 3′ untranslated region and enhances its stability/translation, often doubling protein output. We test this approach on several transcripts associated with haploinsufficiency disorders and increase their steady-state expression in cell culture. We suggest this approach may be a tenable therapeutic modality with precise activity and broad-spectrum application.

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KW - mRNA translation

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Development of a Tethered mRNA Amplifier to increase protein expression

Abstract

Keywords

ASJC Scopus subject areas

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