Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Functional nucleic acids (FNAs) show therapeutic promise but suffer from low serum stability.
• Clinical translation of FNAs is hindered by their degradation in physiological environments.

Purpose of the Study:

• To develop a precise molecular programming strategy for preparing glyconucleic acid aptamers (GNAAs) with enhanced serum stability.
• To evaluate the impact of glycosylation on FNA stability, structure, affinity, and in vivo performance.

Main Methods:

• Designed and synthesized four glyconucleic acid modules for solid-phase synthesis.
• Precisely modified DNA aptamers with carbohydrate ligands at specific sites.
• Assessed serum stability, structural integrity, binding affinity, tumor targeting, and in vivo metabolism.

Main Results:

• Glycosylation significantly increased DNA aptamer serum stability, outperforming commercial modifications.
• Modified aptamers maintained their structures and high affinity for targets.
• The approach showed insignificant effects on in vivo tumor targeting and metabolism.

Conclusions:

• Precise glycosylation is an effective, economical, and efficient strategy to enhance FNA serum stability.
• This method expands the application scope of FNAs in therapeutics.
• Glycosyl functional nucleic acids (GNAAs) are promising for practical therapeutic transformation.