Targeted bioresponsive nucleic acid carriers for efficient delivery

Overview

This solution involves the development of bioresponsive nucleic acid carriers optimized through a bio-inspired chemical evolution strategy. These carriers incorporate artificial amino acids, such as tetraethylene pentamino succinic acid and lipo amino fatty acids, into xenopeptide sequences. The carriers demonstrate remarkable transfection properties both in vitro and in vivo, even in high-serum environments. They are designed for dynamic stability, enabling efficient delivery of various nucleic acids, including pDNA, siRNA, and mRNA, as well as CRISPR/Cas9 components. The carriers show promising pharmacological profiles with low antigenicity, facilitating repeated dosing.

Technical specifications

• Dynamic properties: Double pH-responsive and optionally bioreductive features for efficient delivery.
• Carrier topology: Synthesized in diverse forms—linear, branched, dendritic.
• Endosomal escape: Enhanced delivery efficiency and stability in serum.
• Targeting capabilities: Incorporation of targeting ligands for organ-specific delivery.
• Colloidal stability: Achieved through PEGylation or hyaluronic acid coating.
• Storage and formulation: Optimized for cryoformulation and/or lyoformulation.
• Biochemical characterization: Protein corona analysis post-serum exposure.

Technology readiness level

Currently at Technology Readiness Level 3, this technology has successfully demonstrated its core functionalities in controlled environments. Further development and validation are targeted to enhance stability, targeting, and delivery efficacy, with the goal of advancing to higher readiness levels through in vivo testing and collaboration with external partners.