title: Comparative analysis of DNA nanoparticles and AAVs for ocular gene delivery.
abstract: Gene therapy is a critical tool for the treatment of monogenic retinal diseases. However, the limited vector capacity of the current benchmark delivery strategy, adeno-associated virus (AAV), makes development of larger capacity alternatives, such as compacted DNA nanoparticles (NPs), critical. Here we conduct a side-by-side comparison of self-complementary AAV and CK30PEG NPs using matched ITR plasmids. We report that although AAVs are more efficient per vector genome (vg) than NPs, NPs can drive gene expression on a comparable scale and longevity to AAV. We show that subretinally injected NPs do not leave the eye while some of the AAV-injected animals exhibited vector DNA and GFP expression in the visual pathways of the brain from PI-60 onward. As a result, these NPs have the potential to become a successful alternative for ocular gene therapy, especially for the multitude of genes too large for AAV vectors.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Zongchao
authors.initials: Z
authors.lastname: Han
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.forename: Rasha
authors.initials: R
authors.lastname: Makkia
authors.forename: Junjing
authors.initials: J
authors.lastname: Guo
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cooper
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D012160:Retina / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D049452:Green Fluorescent Proteins; D004247:DNA