Gene Delivered By Nanoparticle System Can Potentially Cure Congenital Blindness Interview with:
Zheng-Rong Lu, Ph.D.

M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering
Department of Biomedical Engineering
Case Western Reserve University
Cleveland, OH 44106 What is the background for this study? What are the main findings?

Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders.

This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered.

In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder. What should readers take away from your report?

Response: Gene therapy holds the promise of delivering a true cure for genetic diseases. Rather than managing the condition, gene therapy addresses the source of the disease by delivering a healthy copy of the mutated gene, which the cells translate into functional protein. Our ECO delivery system is a simple, safe, and effective vehicle to deliver these genes into the correct cells, and can be modified to carry the gene for any monogenic visual disorder. Furthermore, the flexibility of this platform allows for delivery of any type of genetic materials, including RNA and CRISPR/Cas9 gene editing tools. What recommendations do you have for future research as a result of this study?

Response: For all gene therapy systems, a major challenge is to transport and express the gene into the target tissue without affecting other surrounding tissues. To solve this problem, future studies should look into more specific targeting of the delivery systems, and modifying the genes themselves so that they will be expressed only in the targeted cells.

For non-viral gene delivery systems specifically, limited efficiency and transient gene expression mean that multiple injections would be needed to produce a long-term therapeutic effect. Therefore, future studies should focus on improving the transfection efficiency and extending the expression period of the gene. Thank you for your contribution to the community.


Da Sun, Bhubanananda Sahu, Songqi Gao, Rebecca M. Schur, Amita M. Vaidya, Akiko Maeda, Krzysztof Palczewski, Zheng-Rong Lu. Targeted Multifunctional Lipid ECO Plasmid DNA Nanoparticles as Efficient Non-viral Gene Therapy for Leber’s Congenital Amaurosis. Molecular Therapy – Nucleic Acids, 2017; 7: 42 DOI: 10.1016/j.omtn.2017.02.005

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on May 15, 2017 by Marie Benz MD FAAD