Related Experiment Video
Updated: Jun 17, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Enzyme-Responsive DNA Origami-Antibody Conjugates for Targeted and Combined Therapy of Choroidal Neovascularization
1Suzhou Key Laboratory of Nanotechnology and Biomedicine, Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano and Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou 215123, China.
Abstract:
Monotherapy, especially the use of antibodies targeting vascular endothelial growth factor (VEGF), has shown limitations in treating choroidal neovascularization (CNV) since reactive oxygen species (ROS) also exacerbate CNV formation. Herein, we developed a combination therapy based on a DNA origami platform targeting multiple components of ocular neovascularization. Our study demonstrated that ocular neovascularization was markedly suppressed by intravitreal injection of a rectangular DNA origami sheet modified with VEGF aptamers (Ap) conjugated to an anti-VEGF antibody (aV) via matrix metalloproteinase (MMP)-cleavable peptide linkers in a mouse model of CNV. Typically, the DNA origami-based therapeutic platform selectively accumulates in neovascularization lesions owing to the dual-targeting ability of the aV and Ap, followed by the cleavage of the peptide linker by MMPs to release the antibody. Together, the released antibody and Ap inhibited VEGF activity. Moreover, the residual bare DNA origami could effectively scavenge ROS, reducing oxidative stress at CNV sites and thus maximizing the synergistic effects of inhibiting neovascularization.
Insights
This study presents a novel DNA origami platform for treating choroidal neovascularization (CNV). The therapy combines anti-VEGF antibody and aptamers, while the DNA scaffold scavenges reactive oxygen species (ROS) for enhanced treatment.
Area of Science:
- Biotechnology
- Ophthalmology
- Nanomedicine
Background:
- Monotherapy for choroidal neovascularization (CNV) using anti-VEGF antibodies has limitations.
- Reactive oxygen species (ROS) contribute to the exacerbation of CNV.
- A multi-targeted therapeutic approach is needed for effective CNV treatment.
Purpose of the Study:
- To develop and evaluate a DNA origami-based combination therapy for ocular neovascularization.
- To investigate the synergistic effects of targeting VEGF and scavenging ROS in a CNV mouse model.
Main Methods:
- Fabrication of a rectangular DNA origami sheet functionalized with VEGF aptamers (Ap) and an anti-VEGF antibody (aV).
- Conjugation of aV to Ap via matrix metalloproteinase (MMP)-cleavable peptide linkers.
- Intravitreal injection of the DNA origami platform in a mouse model of CNV.
Main Results:
- The DNA origami platform selectively accumulated in neovascularization lesions.
- MMP-cleavable linkers released the antibody, inhibiting VEGF activity.
- The DNA origami scaffold effectively scavenged ROS, reducing oxidative stress and enhancing therapeutic effects.
Conclusions:
- The developed DNA origami platform demonstrates potent suppression of ocular neovascularization.
- This combination therapy offers a synergistic approach by targeting VEGF and mitigating oxidative stress.
- DNA origami nanostructures hold promise as versatile platforms for treating complex ocular diseases like CNV.
More Related Videos
11:02Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
11:58Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
Published on: March 8, 2018
