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DNA Framework-Enabled Ocular Barrier Penetration for Microinvasive Antiangiogenic Therapy
Ruobing Wang1, Yanhan Liu1, Yuelu Zhang2
1Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, and Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Journal of the American Chemical Society
|February 20, 2025
Summary
Tetrahedral framework nucleic acids (tFNAs) enable effective delivery of anti-VEGF aptamers to the eye
Area of Science:
- Biotechnology
- Ophthalmology
- Nanomedicine
Background:
- Therapeutic aptamers targeting vascular endothelial growth factor A (VEGFA) are used for antiangiogenic therapy in choroidal neovascularization (CNV).
- Effective in vivo delivery of aptamers to the eye is challenging due to ocular barriers and degradation.
Purpose of the Study:
- To demonstrate microinvasive delivery of VEGFA-targeted aptamers to the ocular fundus using tetrahedral framework nucleic acids (tFNAs).
- To evaluate the efficacy of aptamer-tFNA conjugates in treating neovascular ophthalmic diseases.
Main Methods:
- Incorporation of anti-VEGFA aptamers into tFNAs to create apt-tFNA conjugates.
- Investigation of apt-tFNA penetration across the outer blood-retinal barrier (oBRB).
- Assessment of antiangiogenic efficacy in a laser-induced CNV mouse model via subconjunctival injection.
Main Results:
- Apt-tFNAs successfully penetrated the oBRB while maintaining structural integrity.
- Apt-tFNAs demonstrated superior inhibition of vascular proliferation and migration by neutralizing VEGFA.
- Subconjunctival injection of apt-tFNA showed comparable efficacy to intravitreal ranibizumab in a CNV mouse model.
Conclusions:
- tFNAs provide an effective method for delivering therapeutic aptamers to the ocular fundus.
- Apt-tFNAs offer a promising approach for microinvasive, periocular administration in treating neovascular eye diseases.
