Engineering fibrinogen-binding VSV-G envelope for spatially- and cell-controlled lentivirus delivery through fibrin hydrogels

Padmashali, Roshan M.; Andreadis, Stelios T.

doi:10.1016/j.biomaterials.2011.01.035

Cited by 28 publications

(26 citation statements)

References 38 publications

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“…Our findings extend previous work showing biomaterialmediated gene delivery using viral vectors (20,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). The majority of this work demonstrated the ability to specify the spatial location of delivered vectors, rather than the induction of tissuespecific differentiation.…”

Section: Discussionsupporting

confidence: 86%

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage

Brunger

Huynh

Guenther

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

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The ability to develop tissue constructs with matrix composition and biomechanical properties that promote rapid tissue repair or regeneration remains an enduring challenge in musculoskeletal engineering. Current approaches require extensive cell manipulation ex vivo, using exogenous growth factors to drive tissue-specific differentiation, matrix accumulation, and mechanical properties, thus limiting their potential clinical utility. The ability to induce and maintain differentiation of stem cells in situ could bypass these steps and enhance the success of engineering approaches for tissue regeneration. The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method. We first showed that poly-L-lysine could immobilize lentivirus to poly(e-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffoldmediated gene delivery of transforming growth factor β3 (TGF-β3), using a 3D woven poly(e-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs. Chondrogenesis induced by scaffold-mediated gene delivery was as effective as traditional differentiation protocols involving medium supplementation with TGF-β3, as assessed by gene expression, biochemical, and biomechanical analyses. Using lentiviral vectors immobilized on a biomechanically functional scaffold, we have developed a system to achieve sustained transgene expression and ECM formation by hMSCs. This method opens new avenues in the development of bioactive implants that circumvent the need for ex vivo tissue generation by enabling the long-term goal of in situ tissue engineering.biomaterials | regenerative medicine | genetic engineering | gene therapy | chondrocyte

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Section: Discussionsupporting

confidence: 86%

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage

Brunger

Huynh

Guenther

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

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“…As a first step to reach that goal, we attempted to display tumor-targeting ligands on a replication-competent VSV. Our approach was to identify novel sites in the G protein of VSV (VSV-G) to insert and display foreign peptides without compromising viral replication kinetics or oncolytic efficacy.Several previous attempts to insert foreign peptides into VSV-G were conducted purely in the interest of lentivirus targeting and purification (17)(18)(19)(20). Additionally, one previous study identified a site that could tolerate insertion of a 16-residue peptide that was an antigenic HIV epitope (21).…”

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confidence: 99%

“…Several previous attempts to insert foreign peptides into VSV-G were conducted purely in the interest of lentivirus targeting and purification (17)(18)(19)(20). Additionally, one previous study identified a site that could tolerate insertion of a 16-residue peptide that was an antigenic HIV epitope (21).…”

mentioning

confidence: 99%

“…RGD has been extensively studied in targeting and killing tumor cells (26). Early studies demonstrated that displaying the RGD peptide on the surface of oncolytic parvoviruses, adenoviruses, or measles viruses enhanced their interaction with tumor vasculature and/or tumor cells (19,27,28). cRGD also has been used to label gold nanoparticles to target tumor cells for destruction or imaging (29,30).…”

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confidence: 99%

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Characteristics of Oncolytic Vesicular Stomatitis Virus Displaying Tumor-Targeting Ligands

Ammayappan

Peng

Russell

2013

J Virol

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bWe sought proof of principle that tumor-targeting ligands can be displayed on the surface of vesicular stomatitis virus (VSV) by engineering its glycoprotein. Here, we successfully rescued VSVs displaying tumor vasculature-targeting ligands. By using a rational approach, we investigated various feasible insertion sites on the G protein of VSV (VSV-G) for display of tumor vasculature-targeting ligands, cyclic RGD (cRGD) and echistatin. We found seven sites on VSV-G that tolerated insertion of the 9-residue cRGD peptide, two of which could tolerate insertion of the 49-amino acid echistatin domain. All of the ligand-displaying viruses replicated as well as the parental virus. In vitro studies demonstrated that the VSVechistatin viruses specifically bound to targeted integrins. Since the low-density lipoprotein receptor (LDLR) was recently identified as a major receptor for VSV, we investigated the entry of ligand-displaying viruses after masking LDLR. The experiment showed that the modified viruses can enter the cell independently of LDLR, whereas entry of unmodified virus is significantly blocked by a specific monoclonal antibody against LDLR. Both parental and ligand-displaying viruses displayed equal oncolytic efficacies in a syngeneic mouse myeloma model. We further demonstrated that single-chain antibody fragments against tumor-specific antigens can be inserted at the N terminus of the G protein and that corresponding replication-competent VSVs can be rescued efficiently. Overall, we demonstrated that functional tumor-targeting ligands can be displayed on replication-competent VSVs without perturbing viral growth and oncolytic efficacy. This study provides a rational foundation for the future development of fully retargeted oncolytic VSVs. V esicular stomatitis virus (VSV) is an enveloped, negativestrand RNA virus that belongs to the Vesiculovirus genus of the Rhabdoviridae family. VSV has the ability to infect and kill cancer cells while sparing normal cells (1-4). Exploitation of this oncolytic property provides a promising alternative approach for the treatment of cancer. For disseminated cancer, virotherapy should ideally be administered systemically (2, 5-7), but this route of delivery brings its own set of problems. The major concerns for VSV virotherapy are neurotoxicity, antibody neutralization, and sequestration in off-target organs, especially the liver and spleen. Many attempts have been made to address these drawbacks. To reduce the neurotoxicity, the matrix protein of VSV was mutated (8, 9), and microRNA targets (10) or picornaviral internal ribosome entry sites (11) were engineered into the VSV genome. Serum neutralization has been avoided by PEGylating the virus (12, 13) or loading onto antigen-specific T cells (14), which ultimately improved virotherapy outcomes.To circumvent all of the above hurdles in a single step, pseudotyping VSV with other viral envelope glycoproteins was considered a potentially feasible approach. Recent studies demonstrated that VSV neurotoxicity can be circumvented by...

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“…Additionally, the reported mesh sizes may not completely prevent the transport of such particles through the mesh. 54,69,70 This measurement provides only an approximation of an idealized meshwork structure, and in reality does not account for network imperfections such as closed polymer loops, dangling ends, and slipping chain entanglements. 71 Interestingly, the profiles of lentivector release and cellular transduction suggest that the mode of gelation and extent of crosslinking may be important parameters in regulating lentivector delivery from microgels.…”

Section: Discussionmentioning

confidence: 99%

Microfluidic generation of alginate microgels for the controlled delivery of lentivectors

et al. 2016

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Microgels fabricated through distinct microfluidic procedures encapsulate and release functioning lentivectors in a controlled manner.Please check this proof carefully. Our staff will not read it in detail after you have returned it.Translation errors between word-processor files and typesetting systems can occur so the whole proof needs to be read. Please pay particular attention to: tabulated material; equations; numerical data; figures and graphics; and references. If you have not already indicated the corresponding author(s) please mark their name(s) with an asterisk. Please e-mail a list of corrections or the PDF with electronic notes attached -do not change the text within the PDF file or send a revised manuscript. Corrections at this stage should be minor and not involve extensive changes. All corrections must be sent at the same time.Please bear in mind that minor layout improvements, e.g. in line breaking, table widths and graphic placement, are routinely applied to the final version.Please note that, in the typefaces we use, an italic vee looks like this: n, and a Greek nu looks like this: n.We will publish articles on the web as soon as possible after receiving your corrections; no late corrections will be made.Please return your final corrections, where possible within 48 hours of receipt, by e-mail to: materialsB@rsc.orgQueries for the attention of the authors However, achieving safe, localized, and sufficient gene expression remain key challenges for effective lentivectoral therapy. Localized and efficient gene expression can be promoted by developing material systems to deliver lentivectors. Here, we address the utility of microgel encapsulation as a strategy for the controlled release of lentivectors. Three distinct routes for ionotropic gelation of alginate were incorporated into microfluidic templating to create lentivector-loaded microgels. Comparisons of the three microgels revealed marked differences in mechanical properties, crosslinking environment, and ultimately lentivector release and functional gene expression in vitro. Gelation with chelated calcium demonstrated low utility for gene delivery due to a loss of lentivector function with acidic gelation conditions. Both calcium carbonate gelation, and calcium chloride gelation, preserved lentivector function with a more sustained transduction and gene expression over 4 days observed with calcium chloride gelated microgels. The validation of these two strategies for lentivector microencapsulation may provide a platform for controlled gene delivery.

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Engineering fibrinogen-binding VSV-G envelope for spatially- and cell-controlled lentivirus delivery through fibrin hydrogels

Cited by 28 publications

References 38 publications

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage

Characteristics of Oncolytic Vesicular Stomatitis Virus Displaying Tumor-Targeting Ligands

Microfluidic generation of alginate microgels for the controlled delivery of lentivectors

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