An Ocular Surface-Targeting Nucleic Acid Hydrogel for Efficient Dry Eye Disease Treatment

Area of Science:

• Biomaterials Science
• Ophthalmology
• Gene Therapy

Background:

• Dry eye disease (DED) affects millions globally, with current treatments inadequately addressing moderate-to-severe cases.
• Existing topical therapies lack effective delivery systems for ocular surface diseases.

Purpose of the Study:

• To develop a targeted nucleic acid hydrogel for effective dry eye disease (DED) treatment.
• To create a delivery system that enhances therapeutic retention and cellular uptake on the ocular surface.

Main Methods:

• An siRNA-embedded nucleic acid hydrogel was engineered, modified with a mucin-1 (MUC1) aptamer for active targeting.
• The hydrogel's adhesive properties and aptamer-mucin interaction were utilized for ocular surface retention.
• Hydrogel degradation into nanoparticles facilitated corneal cell uptake, delivering siRNA to silence the NFKBIZ gene.

Main Results:

• The MUC1 aptamer-modified hydrogel demonstrated enhanced retention on the ocular surface.
• Degradation into nanosized particles improved corneal cell drug uptake.
• siRNA delivery effectively silenced NFKBIZ gene expression, suppressing inflammation and alleviating DED in a mouse model.

Conclusions:

• The developed targeting hydrogel offers a promising strategy for treating dry eye disease.
• This platform demonstrates potential for treating various ocular surface diseases due to its sequence-dependent siRNA delivery mechanism.