RNA Therapeutic Solutions Targeting Condensate

In cells, the attractions that lead to phase separation include RNA-RNA, protein-RNA, DNA-DNA, protein-DNA, and protein-protein interactions. RNA cohesions can be formed in the absence of proteins. RNA relies on RNA length, sequence, structure, modifications, and RNA-RNA/protein interactions to control the phase boundary, composition, and material properties of biomolecular condensates. Given the importance of RNA in phase separation, RNA-based regulation of condensate is possible. RNA interference (RNAi) is a valuable tool for silencing target gene expression and performing large-scale functional genomic screens. Studies have shown that two types of RNAi, small RNA and antisense oligonucleotide (ASO), regulate the phase separation of RNA phases. RNA therapies targeting condensates represent a new class of RNA drugs.

Fig. 1. Regulatory methods of biomolecular condensates. (Conti B A, et al, 2022)

Our Solutions

Using RNA-based condensate regulation capabilities, CD BioSciences is committed to developing RNA therapeutic solutions that target condensates. Our research focuses on the use of direct RNA modification, solubilization of pathological condensates, and synthesis of engineered condensates to restore losses in disease, thus providing new avenues to address a variety of diseases, including but not limited to neurodegenerative diseases.

We offer the following types of RNA therapeutics that target condensates, including:

• RNA as a Modification
  By exploiting the sequence, structure, and modification of RNA, we can precisely modulate its interaction with condensates, thereby altering their composition, properties, and function.
•  RNA Regulates Condensate Composition
  Another approach we are exploring involves the use of RNA to regulate the level of condensate components. By regulating the expression or activity of specific RNA molecules, we can fine-tune the assembly and breakdown of condensates. This targeted regulation allows us to influence the dynamics and stability of condensates, potentially restoring equilibrium to the diseased state.
• mRNAs Encoding IDR-containing Proteins or Phase Modifiers
  We can use mRNAs encoding proteins containing intrinsically disordered regions (IDRs) to influence the behavior of condensates. By introducing these proteins into the cell, we aim to promote or disrupt the assembly of condensates depending on the specific therapeutic target.
• Aptamer Binding to IDR-containing Proteins or Phase Separation Regulators
  Aptamers are short RNA or DNA molecules that selectively bind specific target proteins or regulators. We can use aptamers with high affinity and specificity for these targets, and we can control the behavior and properties of the cohesin.

Our experts rationalize RNA modifications to maximize RNA stability and minimize RNA immunogenicity. The primary goal of these strategies is to modify or solubilize pathological condensates associated with various diseases. CD BioSciences is at the forefront of RNA therapeutic solutions for condensates, leveraging the emerging field of phase separation and RNA therapy to develop innovative drugs. By leveraging the control of phase separation by RNA, we aim to revolutionize the therapeutic landscape by providing precise and effective treatments for multiple conditions. If you are interested in our solutions, please contact us now.