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Editor’s Choice
Nanotechnology for Gene Delivery to the Eye
Swita R Singh
1
and Uday B Kompella
2
1. Formulation Scientist, Wyeth Pharmaceuticals; 2. Professor of Pharmaceutical Sciences and Ophthalmology, University of Colorado, Denver
Abstract
The relatively immune-privileged status of the eye makes it an interesting target for gene delivery. Gene delivery to the eye using viral
vectors via subretinal and intravitreal injections has been extensively investigated. Recently, the safety of recombinant adeno-associated
virus vector expressing RPE65 complementary DNA (cDNA) in a limited clinical trial of three patients has also been reported.
Nanotechnology-based non-viral vectors offer the advantages of safety and flexibility in terms of loading capacity and delivery system
design compared with viral vectors. An ideal non-viral vector should be non-toxic, efficiently taken up into the target cells and conducive
to gene expression, and should protect the gene against enzymatic degradation. Multiple kinds of nanotechnology-based non-viral vectors
have been investigated for potential applications for gene delivery to the eye, namely nanoplexes, dendrimers, micelles, nanoparticles and
liposomes. This article summarises and discusses key advances in the application of nanotechnology for gene delivery to the eye.
Keywords
Nanotechnology, gene delivery, eye, nanoparticles, liposomes
Disclosure: The authors have a patent pending for functionalised nanoparticles for the eye.
Received: 20 April 2009 Accepted: 6 May 2009
Correspondence: Uday B Kompella, Department of Pharmaceutical Sciences, University of Colorado, Denver, 12700 East 19th Avenue, Aurora, CO 80045, US.
E:
uday.kompella@ucdenver.edu
Gene therapy is a promising therapeutic approach for the treatment expression, and should protect the gene against enzymatic
of a wide array of inherited and acquired disorders. The eye is a degradation. In this article, potential routes of administration for
particularly interesting target for gene delivery owing to the gene delivery to the eye and examples of nanotechnology-based
relatively immune-privileged status of the tissue. In the eye, gene nano-size non-viral vectors for ocular gene delivery are discussed.
delivery has potential applications in treating various disorders
including neovascular and non-neovascular retinal degenerative Routes of Administration for
disorders, glaucoma and corneal graft rejection, among others. Gene Delivery to the Eye
Indeed, a number of viral vectors have been shown to successfully Gene delivery to the eyes using non-viral nanotechnology-based
result in intraocular gene expression.
1
vectors can be achieved by multiple routes of administration.
4
The
various routes assessed for this purpose include topical,
5
Recently, Bainbridge et al.
2
published the results of a three-patient intracameral,
5
intracorneal,
6
subconjunctival,
7
intravitreal,
8,9
clinical trial conducted to assess the safety of subretinally delivered subretinal
10–12
and intravenous
13–16
(see Figure 1). The choice of route
recombinant adeno-associated virus vector expressing RPE65 of administration is based on the target tissue within the eye. For
complementary DNA (cDNA). The study concluded that the vectors gene expression in the anterior segment, topical, intracameral and
were largely safe. The safety and efficacy of viral vectors must be intracorneal routes may be employed. For gene expression in the
further established in larger clinical trials to enable their clinical posterior segment of the eye, intravitreal and subretinal injections
acceptance. In the study by Bainbridge et al., although none of are most commonly used. Subconjunctival and peri-ocular
the patients showed significant improvement in visual acuity, one injections can potentially deliver the vectors or the expressed
patient showed improvement in visual function on microperimetry proteins to the anterior as well as the posterior segment of the eye.
and dark-adapted perimetry and in a subjective test of mobility. Yoon et al.
7
reported transfection of corneal cells after
Thus, clinical use of gene therapy is challenged by effective gene subconjunctival injection of liposomes loaded with a plasmid
delivery in vivo. In addition, viral vectors have the drawback of encoding the extracellular region of brain-specific angiogenesis
limited gene-carrying capacity, immunogenicity and toxicity.
3
inhibitor 1 (BAI1-ECR) in rabbits. Plasmid expression was observed
in corneal stroma for seven days. The intravenous route of
For these reasons, our group and several other investigators are administration for ocular delivery is usually not preferred
investigating the use of non-viral vectors as an alternative to viral because of the presence of blood ocular barriers; however, the
vectors. An ideal non-viral gene delivery vector should be non-toxic, intravenous route is now being increasingly investigated for gene
efficiently taken up by target cells and conducive to gene delivery purposes.
© TOUCH BRIEFINGS 2009 7
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