Structure-Activity Relationships in Nucleic-Acid-Templated Vectors Based on Peptidic Dynamic Covalent Polymers

Area of Science:

• Biomaterials Science
• Gene Delivery Systems
• Polymer Chemistry

Background:

• Nucleic acid templated self-assembly offers a versatile method for creating tailored delivery vectors.
• Understanding the structure-activity relationships in these self-assembly processes is crucial but remains poorly understood.

Purpose of the Study:

• To investigate the structure-activity relationships of arginine-rich dynamic covalent polymers (DCPs) for nucleic acid delivery.
• To identify specific DCP compositions that enable efficient nucleic acid complexation and delivery.

Main Methods:

• Synthesis and characterization of arginine-rich DCPs with varying arginine content and positions.
• Evaluation of nucleic acid complexation with different templates (siRNA, DNA) in saline buffer.
• In vitro testing of DCPs for safe and effective siRNA delivery in live cancer cells.

Main Results:

• Several arginine-rich DCPs demonstrated nucleic acid complexation capabilities with both short siRNA and long DNA templates.
• A specific peptidic DCP, featuring a six-arginine repeating unit, was identified as highly effective.
• This optimized DCP facilitated safe and effective delivery of siRNA in live cancer cells.

Conclusions:

• Arginine-rich DCPs represent a promising platform for self-fabricating nucleic acid delivery vectors.
• The identified six-arginine DCP shows significant potential for advancing gene therapy applications through effective siRNA delivery.
• Further exploration of structure-activity relationships can lead to improved nucleic acid delivery systems.