RNA-Polymer Conjugates via Direct Incorporation of the Chain Transfer Agent and PET-RAFT Polymerization

Area of Science:

• Bioconjugation Chemistry
• Polymer Science
• RNA Modification

Background:

• Covalent conjugation of RNA with synthetic polymers offers enhanced properties but is limited by complex, solid-phase synthesis methods.
• Existing techniques require pre-installed functional groups on RNA, hindering practical applications and scalability.

Purpose of the Study:

• To develop a novel, direct method for synthesizing RNA-polymer conjugates.
• To overcome the limitations of conventional solid-phase synthesis for RNA modification.
• To enhance the accessibility of functional RNA-polymer materials.

Main Methods:

• Synthesized a chain transfer agent (CTA)-functionalized acyl imidazole reagent for direct RNA modification.
• Utilized acylation chemistry to covalently attach the CTA to RNA's 2'-hydroxyl groups.
• Employed reversible addition-fragmentation chain transfer (RAFT) polymerization, using RNA-CTA as a macro-CTA for direct grafting-from RNA synthesis.

Main Results:

• Achieved direct, postsynthetic modification of synthetic and biomass RNAs.
• Produced RNA-polymer conjugates with controlled molecular weight and low dispersity.
• Demonstrated the creation of thermoresponsive conjugates and biodegradable hydrogels from biomass RNA.

Conclusions:

• The novel acylation and RAFT polymerization approach enables direct RNA-polymer conjugation, bypassing solid-phase synthesis.
• This method significantly improves the accessibility of functional RNA-polymer materials, including those derived from biomass.
• The developed strategy opens new avenues for creating advanced bioconjugates and functional materials.