Nanoparticle-based technologies for retinal gene therapy

Adijanto, Jeffrey; Naash, Muna I.

doi:10.1016/j.ejpb.2014.12.028

Cited by 81 publications

(60 citation statements)

References 232 publications

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“…There are several types of NPs including metal-, lipid-, and polymer-based systems. They are different in size, charge, and structure but are all able to enter the cells, while avoiding the endosomes, and transfer the vector into the nucleus for gene expression (Adijanto and Naash, 2015). NPs allow combining several different plasmids in one particle to increase transgene expression (Klausner et al, 2010).…”

Section: Corneal Epithelial Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

608

554

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Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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Section: Corneal Epithelial Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

608

554

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“…For example, polyethylene glycol-substituted polylysine (CK30PEG) NPs (further discussed below) have been used in several disease models (for review see (72)). These NPs are non-toxic, non-immunogenic and have no adverse effects on the retina after subretinal injection in wildtype mice or mice with retinal degeneration (73, 74), and importantly have a large carrying capacity (tested up to 14 kbp in the eye (75) and up to 20 kbp in the lung (76)).…”

Section: Therapeutic Approaches For Ocular Diseases With Gene Thermentioning

confidence: 99%

Non-viral therapeutic approaches to ocular diseases: An overview and future directions

Zulliger

Conley

Naash

2015

Journal of Controlled Release

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Currently there are no viable treatment options for patients with debilitating inherited retinal degeneration. The vast variability in disease-inducing mutations and resulting phenotypes has hampered the development of therapeutic interventions. Gene therapy is a logical approach, and recent work has focused on ways to optimize vector design and packaging to promote optimized expression and phenotypic rescue after intraocular delivery. In this review, we discuss ongoing ocular clinical trials, which currently use viral gene delivery, but focus primarily on new advancements in optimizing the efficacy of non-viral gene delivery for ocular diseases. Non-viral delivery systems are highly customizable, allowing functionalization to improve cellular and nuclear uptake, bypassing cellular degradative machinery, and improving gene expression in the nucleus. Non-viral vectors often yield transgene expression levels lower than viral counterparts, however their favorable safety/immune profiles and large DNA capacity (critical for the delivery of large ocular disease genes) make their further development a research priority. Recent work on particle coating and vector engineering present exciting ways to overcome limitations of transient/low gene expression levels, but also highlight the fact that further refinements are needed before use in the clinic.

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“…RP is associated with more than 100 mutations 12 in the different regions of the rhodopsin (Rho) gene that accounts for 30–40% of adRP 10 , and thus is genetically heterogeneous 3, 5, 10 . Rhodopsin protein helps to keep the structural integrity of the rod outer segments, as it was observed that Rho −/− mice were not able to extend rod outer segments.…”

Section: Ocular Disordersmentioning

confidence: 99%

Nanoparticle‐motivated gene delivery for ophthalmic application

Mitra

Zheng

Han

2015

WIREs Nanomed Nanobiotechnol

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Ophthalmic gene therapy is an intellectual and intentional manipulation of desired gene expression into the specific cells of an eye for the treatment of ophthalmic (ocular) genetic dystrophies and pathological conditions. Exogenous nucleic acids such as DNA, small interfering RNA (siRNA), micro RNA (miRNA), etc., are used for the purpose of managing expression of the desired therapeutic proteins in ocular tissues. The delivery of unprotected nucleic acids into the cells is limited due to exogenous and endogenous degradation modalities. Nanotechnology, a promising and sophisticated cutting edge tool, works as a protective shelter for these therapeutic nucleic acids. They are able to be safely delivered to the required cells in order to modulate anticipated protein expression. To this end, nanotechnology is seen as a potential and promising strategy in the field of ocular gene delivery. This review focused on current nanotechnology modalities and other promising non-viral strategies being used to deliver therapeutic genes in order to treat various devastating ocular diseases.

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Nanoparticle-based technologies for retinal gene therapy

Cited by 81 publications

References 232 publications

Progress in corneal wound healing

Progress in corneal wound healing

Non-viral therapeutic approaches to ocular diseases: An overview and future directions

Nanoparticle‐motivated gene delivery for ophthalmic application

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