Reprogramming Virus Nanoparticles to Bind Metal Ions upon Activation with Heat

Musick, Matthew; McConnell, Kellie I.; Lue, Jerry K.; Wei, Fang; Chen, Clive; Suh, Junghae

doi:10.1021/bm200225x

Cited by 8 publications

(12 citation statements)

References 23 publications

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“…[1][2][3][4][5] In recent years, nonviral methods for delivery have received particular attention due to immunogenic and toxic responses associated with viral vectors, which limit practical use and tenability. [6][7][8] One important limitation of nonviral gene delivery is the inefficient delivery of functional nucleic acids to the nucleus.…”

mentioning

confidence: 99%

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres

Pandit

Watson

Ren

et al. 2015

Tissue Engineering Part C: Methods

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Polycationic nanocomplexes are a robust means for achieving nucleic acid condensation and efficient intracellular gene deliveries. To enhance delivery, a multilayered nanoparticle consisting of a core of electrostatically bound elements was used. These included a histone-mimetic peptides, poly-l-arginine and poly-d-glutamic acid was coated with silicate before surface functionalization with poly-l-arginine. Transfection efficiencies and duration of expression were similar when using green fluorescent protein (GFP) plasmid DNA (pDNA) or GFP mRNA. These nanoparticles demonstrated significantly higher ( > 100%) and significantly longer (15 vs. 4 days) transfection efficiencies in comparison to a commercial transfection agent (Lipofectamine 2000). Reprogramming of human foreskin fibroblasts using mRNA to the Sox2 transcription factor resulted in three-fold higher neurosphere formation in comparison to the commercial reagent. These results demonstrate the potential of these nanoparticles as ideal vectors for gene delivery.

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mentioning

confidence: 99%

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres

Pandit

Watson

Ren

et al. 2015

Tissue Engineering Part C: Methods

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“…While engineering the AAV capsid allows for avoiding immune recognition and redirecting tissue tropism, it may affect binding to cells, intracellular trafficking, and nucleic acid unpackaging, potentially leading to a decrease in AAV transduction efficacy. , Repeated administration could potentially induce an adaptive immune response, with the development of nAbs against altered capsids, and transcapsidation may not guarantee success in avoiding immune recognition as cross-recognition of different serotypes exists. , Despite the previous notion that there is preferential packing of AAV serotypes within their respective capsids, cross-packaging and mosaicism via directed evolution were found to be surprisingly common at generating inhomogeneous capsids. , Light-activated AAV showed a degree of cytotoxicity, and the requirement for existing PhyB-NLS in a target cell may limit its suitability to only in vitro transduction applications …”

Section: Methods Of Aav Engineeringmentioning

confidence: 99%

Synthetically Engineered Adeno-Associated Virus for Efficient, Safe, and Versatile Gene Therapy Applications

2020

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Gene therapy directly targets mutations causing disease, allowing for a specific treatment at a molecular level. Adeno-associated virus (AAV) has been of increasing interest as a gene delivery vehicle, as AAV vectors are safe, effective, and capable of eliciting a relatively contained immune response. With the recent FDA approval of two AAV drugs for treating rare genetic diseases, AAV vectors are now on the market and are being further explored for other therapies. While showing promise in immune privileged tissue, the use of AAV for systemic delivery is still limited due to the high prevalence of neutralizing antibodies (nAbs). To avoid nAb-mediated inactivation, engineered AAV vectors with modified protein capsids, materials tethered to the capsid surface, or fully encapsulated in a second, larger carrier have been explored. Many of these engineered AAVs have added benefits, including avoided immune response, overcoming the genome size limit, targeted and stimuliresponsive delivery, and multimodal therapy of two or more therapeutic modalities in one platform. Native and engineered AAV vectors have been tested to treat a broad range of diseases, including spinal muscular atrophy, retinal diseases, cancers, and tissue damage. This review will cover the benefits of AAV as a promising gene vector by itself, the progress and advantages of engineered AAV vectors, particularly synthetically engineered ones, and the current state of their clinical translation in therapy.

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“…23 There has been an approach to reprogramming AAV to enable the surface exposure of metal binding motifs upon heating. 24 Nevertheless, the source of such virus is limited, and the biomodification of the structures is difficult. Reprogramming the virus provides an attractive method, but the cost is much higher as compared with the synthetic polymeric systems.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Such conformational change is also found for many other parvoviruses, and this property plays a major role in infectivity . There has been an approach to reprogramming AAV to enable the surface exposure of metal binding motifs upon heating . Nevertheless, the source of such virus is limited, and the biomodification of the structures is difficult.…”

Section: Introductionmentioning

confidence: 99%

Protein Nanogels with Temperature-Induced Reversible Structures and Redox Responsiveness

Zhang

Xing

et al. 2016

ACS Biomater. Sci. Eng.

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There are many natural examples of smart structures that are able to change conformations and functionalities responding to the external stimuli. The responsiveness is directly related to their unique structures. In the design of new materials, it is crucial to endow these materials with the capabilities to change structures and functionalities under the external stimuli. In this research, virus-mimicking protein nanogels with temperature-induced reversible structures and redox responsiveness are synthesized by cross-linking a thermally responsive polymer poly(di(ethylene glycol) methyl ether methacrylate-co-2-(2-pyridyldisulfide) ethyl methacrylate) with reduced bovine serum albumin (BSA) molecules through thiol−disulfide exchange reaction. The lower critical solution temperature (LCST) and sizes of the nanogels can be controlled by controlling the reaction conditions. The nanogels are able to change their structures responding to the temperature change. Below the LCST, BSA molecules are embedded inside the nanogels and protected by the polymer chains. Above the LCST, polymer chains collapse forming the cores, and BSA moves to the shells to stabilize the nanogels. The disulfide-cross-linked nanogels are dissociated in the presence of glutathione. In vitro cytotoxicity assays and cell uptake assays demonstrate that the nanogels show low toxicity toward 3T3, 293T, and MCF-7 cells and can be internalized into the MCF-7 cells. The nanogels will find applications in protein delivery.

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Reprogramming Virus Nanoparticles to Bind Metal Ions upon Activation with Heat

Cited by 8 publications

References 23 publications

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres

Synthetically Engineered Adeno-Associated Virus for Efficient, Safe, and Versatile Gene Therapy Applications

Protein Nanogels with Temperature-Induced Reversible Structures and Redox Responsiveness

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