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Synthesis and Characterization of Glycol Chitosan DNA Nanoparticles for Retinal Gene Delivery
Author(s) -
Mitra Rajendra N.,
Han Zongchao,
Merwin Miles,
Al Taai Muhammed,
Conley Shan M.,
Naash Muna I.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300371
Subject(s) - gene delivery , retinal , genetic enhancement , green fluorescent protein , plasmid , transfection , microbiology and biotechnology , chemistry , dna , chitosan , saline , biophysics , gene , biology , biochemistry , endocrinology
Abstract Given the number of monogenic ocular diseases and the number of non‐monogenic degenerative ocular diseases for which gene therapy is considered as a treatment, the development of effective therapeutic delivery strategies for DNA is a critical research goal. In this work, nonviral nanoparticles (NPs) composed of glycol chitosan (GCS) and plasmid DNA (pDNA) were generated, characterized, and evaluated. These particles are stable, do not aggregate in saline, are resistant to DNases, and have a hydrodynamic diameter of approximately 250 nm. Furthermore, the plasmid in these NPs was shown to maintain its proper conformation and can be released and expressed inside the cell. To determine whether these NPs would be suitable for intraocular use, pDNA carrying the ubiquitously expressed CBA‐eGFP expression cassette was compacted and subretinally injected into adult wild‐type albino mice. At day 14 post‐injection (PI), substantial green fluorescent protein (GFP) expression was observed exclusively in the retinal pigment epithelium (RPE) in eyes treated with GCS NPs but not in those treated with uncompacted pDNA or vehicle (saline). No signs of gross retinal toxicity were observed, and at 30 days PI, there was no difference in electroretinogram function between GCS NP‐, pDNA‐, or vehicle‐treated eyes. These results suggest that with further development, GCS NPs could be a useful addition to the available repertoire of genetic therapies for the treatment of RPE‐associated diseases.