Triazine-Modified Oligonucleotides for Cell Penetration and Stability

The patent modifies the phosphate group parameters (charge, structure) by introducing triazine moieties and varying substituents (R1-R6) to change the chemical properties of the oligonucleotide backbone. This allows maintaining synthesis compatibility while improving cell penetration through parameter optimization of the phosphate group characteristics.

The patent creates composite phosphate group structures combining triazine rings with various substituents (alkyl, aryl, heteroaryl groups) to form hybrid molecules that integrate the benefits of both the triazine core structure and the functional substituents, achieving enhanced cell penetration while remaining compatible with standard synthesis.

The patent designs a universal modification approach where a single triazine-phosphate group structure can be incorporated at different positions in the oligonucleotide sequence using standard phosphoramidite chemistry. This multi-functional modification (improving penetration, stability, and binding) can be applied consistently across different oligonucleotide products without requiring separate synthesis protocols for each application.

The patent applies the phosphate group modification locally at specific positions within the oligonucleotide sequence rather than uniformly throughout. This allows optimization of therapeutic potential at critical binding sites while maintaining standard synthesis procedures for the rest of the molecule, thereby reducing overall production complexity.

The patent uses triazine-phosphate groups as intermediary structures that can be introduced through standard phosphoramidite intermediates. The triazine moiety acts as a stable bridge between the phosphate backbone and the functional substituents, providing chemical stability while allowing the use of conventional synthesis intermediates that do not require exceptional manufacturing precision.

The patent performs preliminary synthesis of the triazine-phosphate building blocks before incorporating them into the full oligonucleotide sequence. This preliminary action allows for optimization and quality control of the stable triazine-phosphate unit in isolation, ensuring that once incorporated, it maintains its stability without requiring ultra-precise manufacturing conditions during the final assembly.