Non-viral strategies for ocular gene delivery

Oliveira, Ana V.; Costa, Ana M. Rosa da; Silva, Gabriela A.

doi:10.1016/j.msec.2017.04.068

Cited by 66 publications

(53 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, to induce the formation of new blood vessels and to promote the reconstruction of a mature vascular network, both the VEGF165 and Ang‐1 genes were selected and loaded into SF scaffolds to infect cells and coexpress bioactive VEGF165 and Ang‐1 in situ. Although gene‐activated scaffolds with nonviral gene vectors present the potential to promote vascularization, the low transfection efficiency of nonviral vectors has limited their therapeutic application (Oliveira, Rosa da Costa, & Silva, ; Reckhenrich et al, ; Wang et al, ). Recombinant adenoviruses have been used for gene therapy without integration into the host system (Appaiahgari & Vrati, ; F. C. Zhu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration

Wang

Jiang

et al. 2019

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Vascularization remains a critical challenge in dermal tissue regeneration. In this study, a vascular endothelial growth factor (VEGF165) and angiopoietin‐1 (Ang‐1) dual gene coexpression vector that encoded green fluorescent protein (GFP) was constructed from an arginine–glycine–aspartic acid‐modified adenovirus. Silk fibroin (SF) scaffolds loaded with adenovirus vectors were fabricated by freeze‐drying method. In vitro, the human endothelial‐derived cell line EA.hy926 was infected with adenovirus vectors and then expressed GFP, secreted VEGF165 and Ang‐1, and promoted cell proliferation effectively. The VEGF165 and Ang‐1 genes loaded in the SF scaffolds significantly promoted the formation of abundant microvascular networks in the chick embryo chorioallantoic membrane. In vivo, angiogenic genes loaded in the scaffolds promoted vascularization and collagen deposition in scaffolds, thus effectively accelerating dermal tissue regeneration in a dorsal full‐thickness skin defect wound model in Sprague–Dawley rats. In conclusion, SF scaffolds loaded with arginine–glycine–aspartic acid‐modified adenovirus vectors encoding VEGF165 and Ang‐1 could stimulate the formation of vascular networks through the effective expression of target genes in vascular endothelial cells, thereby accelerating the regeneration of dermal tissue.

show abstract

Section: Discussionmentioning

confidence: 99%

Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration

Wang

Jiang

et al. 2019

J Tissue Eng Regen Med

View full text Add to dashboard Cite

show abstract

“…While non-viral IL-10 gene therapy has been shown to effectively relieve pathological pain in numerous animal models, initial studies required repeated large doses of DNA, thereby making clinical translation less feasible. To ameliorate the dose limitations, various carriers for non-viral gene therapy have been explored but are limited by adverse effects or added levels of complexity (71,72,141). Co-delivered adjuvants may offer a simpler alternative to carrier-type approaches.…”

Section: Adjuvants For Non-viral Gene Therapymentioning

confidence: 99%

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

2019

View full text Add to dashboard Cite

Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain management. In this review we first offer an overview of the relationships between pro-inflammatory cytokine and chemokine signaling and pathological pain, with a focus on the actions of cytokines and chemokines in communication between glia (astrocytes and microglia), immune cells (macrophages and T cells), and neurons. These interactions will be discussed in relation to both peripheral and central nervous system locations. Several novel non-neuronal drug targets for controlling pain are emerging as highly promising, including non-viral IL-10 gene therapy, which offer the potential for substantial pain relief through localized modulation of targeted cytokine pathways. Preclinical investigation of the mechanisms underlying the success of IL-10 gene therapy revealed the unexpected discovery of the powerful anti-nociceptive anti-inflammatory properties of D-mannose, an adjuvant in the non-viral gene therapeutic formulation. This review will include gene therapeutic approaches showing the most promise in controlling pro-inflammatory signaling via increased expression of anti-inflammatory cytokines like interleukin-10 (IL-10) or IL-4, or by directly limiting the bioavailability of specific pro-inflammatory cytokines, as with tumor necrosis factor (TNF) by the TNF soluble receptor (TNFSR). Approaches that increase endogenous anti-inflammatory signaling may offer additional opportunities for pain therapeutic development in patients not candidates for gene therapy. Promising novel avenues discussed here include the disruption of lymphocyte function-associated antigen (LFA-1) activity, antagonism at the cannabinoid 2 receptor (CB2R), and toll-like receptor 4 (TLR4) antagonism. Given the partial efficacy of current drugs, new strategies to manipulate neuroimmune and cytokine interactions hold considerable promise.

show abstract

“…Non-viral vector therapy relies on physical methods (mechanical, electrical, or surgical procedures) that deliver naked DNA, or chemical methods (high salt solutions and polycation carriers) that enhance entry of nucleic acid into cells [1,10,[12][13][14]. Naked DNA is quite unstable, and thus a variety of non-viral nanocarriers based on inorganic particles, liposomes, and cationic lipids and polymers (e.g., polylysine, polyarginine, chitosan) have been proposed [4,15]. Typically, non-viral vectors may establish electrostatic interactions with both the nucleic acid (forming complexes) and the cell surface facilitating attachment and subsequent endocytosis [16].…”

Section: Introductionmentioning

confidence: 99%

Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy

et al. 2020

View full text Add to dashboard Cite

As an alternative to eye drops and ocular injections for gene therapy, the aim of this work was to design for the first time hydrogel contact lenses that can act as platforms for the controlled delivery of viral vectors (recombinant adeno-associated virus, rAAV) to the eye in an effective way with improved patient compliance. Hydrogels of hydroxyethyl methacrylate (HEMA) with aminopropyl methacrylamide (APMA) (H1: 40, and H2: 80 mM) or without (Hc: 0 mM) were synthesized, sterilized by steam heat (121 °C, 20 min), and then tested for gene therapy using rAAV vectors to deliver the genes to the cornea. The hydrogels showed adequate light transparency, oxygen permeability, and swelling for use as contact lenses. Loading of viral vectors (rAAV-lacZ, rAAV-RFP, or rAAV-hIGF-I) was carried out at 4 °C to maintain viral vector titer. Release in culture medium was monitored by fluorescence with Cy3-rAAV-lacZ and AAV Titration ELISA. Transduction efficacy was tested through reporter genes lacZ and RFP in human bone marrow derived mesenchymal stem cells (hMSCs). lacZ was detected with X-Gal staining and quantified with Beta-Glo®, and RFP was monitored by fluorescence. The ability of rAAV-hIGF-I-loaded hydrogels to trigger cell proliferation in hMSCs was evaluated by immunohistochemistry. Finally, the ability of rAAV-lacZ-loaded hydrogels to transduce bovine cornea was confirmed through detection with X-Gal staining of β-galactosidase expressed within the tissue.

show abstract

Non-viral strategies for ocular gene delivery

Cited by 66 publications

References 115 publications

Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration

Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy

Contact Info

Product

Resources

About