Biomolecular condensates: new opportunities for drug discovery and RNA therapeutics

Conti, Brooke A.; Oppikofer, Mariano

doi:10.1016/j.tips.2022.07.001

Cited by 31 publications

(22 citation statements)

References 145 publications

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“…The importance of RNA condensation in studying cellular functions as well as disease diagnosis and treatment has been increasingly recognized. 11,31 Programmable and selffunctional probes that enable precise cellular RNA condensate regulation are thus useful tools in the field of chemical biology and synthetic biology. In this study, we demonstrated that naturally existing CAG repeats can be used as genetically encoded tags to induce cellular condensation of different RNAs of interest, including small noncoding RNAs and long mRNAs (>3,000 nt).…”

Section: Discussionmentioning

confidence: 99%

Targeted RNA Condensation in Living Cells via Genetically Encodable Triplet Repeat Tags

Xue

Sun

et al. 2023

Preprint

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Living systems contain various functional membraneless organelles that can segregate selective proteins and RNAs via liquid-liquid phase separation. Inspired by nature, many synthetic compartments have been engineered in vitro and in living cells, mostly focused on protein-scaffolded systems. Herein, we introduce a nature-inspired genetically encoded RNA tag to program cellular condensate formations and recruit non-phase-transition target RNAs to achieve functional modulation. In our system, different lengths of CAG-repeat tags were tested as the self-assembled scaffold to drive multivalent condensate formation. Various selective target messenger RNAs and noncoding RNAs can be compartmentalized into these condensates. With the help of fluorogenic RNA aptamers, we have systematically studied the formation dynamics, spatial distributions, sizes, and densities of these cellular RNA condensates. The regulation functions of these CAG-repeat tags on the cellular RNA localization, lifetime, RNA-protein interactions, and gene expression have also been investigated. Considering the importance of RNA condensation in both health and disease conditions, these genetically encodable modular and self-assembled tags can be potentially widely used for chemical biology and synthetic biology studies.

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Section: Discussionmentioning

confidence: 99%

Targeted RNA Condensation in Living Cells via Genetically Encodable Triplet Repeat Tags

Xue

Sun

et al. 2023

Preprint

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“…We propose that a better mechanistic understanding of c-mod action and the thoughtful application of condensate science may enable improvements in existing drugs and the discovery of novel classes of drugs. Additionally, this new vantage point enables access to a new pool of targets, historically considered “undruggable,” including proteins with high levels of structural dynamics and RNA (reviewed in ( Conti and Oppikofer, 2022 ; Mitrea et al, 2022 )).…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Principles and functions of condensate modifying drugs

Patel¹,

Mitrea²,

Namasivayam

et al. 2022

Front. Mol. Biosci.

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Biomolecular condensates are compartmentalized communities of biomolecules, which unlike traditional organelles, are not enclosed by membranes. Condensates play roles in diverse cellular processes, are dysfunctional in many disease states, and are often enriched in classically “undruggable” targets. In this review, we provide an overview for how drugs can modulate condensate structure and function by phenotypically classifying them as dissolvers (dissolve condensates), inducers (induce condensates), localizers (alter localization of the specific condensate community members) or morphers (alter the physiochemical properties). We discuss the growing list of bioactive molecules that function as condensate modifiers (c-mods), including small molecules, oligonucleotides, and peptides. We propose that understanding mechanisms of condensate perturbation of known c-mods will accelerate the discovery of a new class of therapies for difficult-to-treat diseases.

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“…In recent years, their role was implicated in several biochemical processes, in physiology and disease 2 . Consequently, biomolecular condensates are now leveraged as a new class of therapeutic targets 3 , 4 .…”

Section: Mainmentioning

confidence: 99%

CD-CODE: crowdsourcing condensate database and encyclopedia

et al. 2023

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The discovery of biomolecular condensates transformed our understanding of intracellular compartmentalization of molecules. To integrate interdisciplinary scientific knowledge about the function and composition of biomolecular condensates, we developed the crowdsourcing condensate database and encyclopedia (cd-code.org). CD-CODE is a community-editable platform, which includes a database of biomolecular condensates based on the literature, an encyclopedia of relevant scientific terms and a crowdsourcing web application. Our platform will accelerate the discovery and validation of biomolecular condensates, and facilitate efforts to understand their role in disease and as therapeutic targets.

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Biomolecular condensates: new opportunities for drug discovery and RNA therapeutics

Cited by 31 publications

References 145 publications

Targeted RNA Condensation in Living Cells via Genetically Encodable Triplet Repeat Tags

Targeted RNA Condensation in Living Cells via Genetically Encodable Triplet Repeat Tags

Principles and functions of condensate modifying drugs

CD-CODE: crowdsourcing condensate database and encyclopedia

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