Open AccessComparative Analysis of DNA Nanoparticles and AAVs for Ocular Gene Delivery
Author(s) -
Zongchao Han,
Shan M. Conley,
Rasha Makkia,
Jun Guo,
Mark J. Cooper,
Muna I. Naash
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0052189
Subject(s) - gene delivery , genetic enhancement , adeno associated virus , vector (molecular biology) , gene , plasmid , viral vector , biology , dna , transfection , gene expression , computational biology , genetics , recombinant dna
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.