A reduction in the human adenovirus virion size through use of a shortened fibre protein does not enhance muscle transduction following systemic or localised delivery in mice

McFall, Emily; Murray, Lyndsay M.; Lunde, John A.; Jasmin, Bernard J.; Kothary, Rashmi; Parks, Robin J.

doi:10.1016/j.virol.2014.08.026

Cited by 6 publications

(3 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To investigate the direct relationship between muscular myogenin and spinal motor neuron survival, we overexpressed myogenin in NRIP cKO gastrocnemius muscles by intramuscular Ad‐myogenin injection. Although intramuscular inoculation of certain adenoviral vectors might lead to retrograde gene expression in spinal motor neurons, we found myogenin overexpressed in muscles but not the spinal cord after Ad‐myogenin treatment (data not shown). On muscle‐restricted overexpression of myogenin in mice, muscle defects were improved and the NMJ architecture restored.…”

Section: Discussionsupporting

confidence: 82%

Muscle‐restricted nuclear receptor interaction protein knockout causes motor neuron degeneration through down‐regulation of myogenin at the neuromuscular junction

Chen

Tsai

Liao

et al. 2018

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

BackgroundNuclear receptor interaction protein (NRIP) is a calcium/calmodulin (CaM) binding protein. Nuclear receptor interaction protein interacts with CaM to activate calcineurin and CaMKII signalling. The conventional NRIP knockout mice (global knockout) showed muscular abnormality with reduction of muscle oxidative functions and motor function defects.MethodsTo investigate the role of NRIP on neuromuscular system, we generated muscle‐restricted NRIP knockout mice [conditional knockout (cKO)]. The muscle functions (including oxidative muscle markers and muscle strength) and lumbar motor neuron functions [motor neuron number, axon denervation, neuromuscular junction (NMJ)] were tested. The laser‐captured microdissection at NMJ of skeletal muscles and adenovirus gene therapy for rescued effects were performed.ResultsThe cKO mice showed muscular abnormality with reduction of muscle oxidative functions and impaired motor performances as global knockout mice. To our surprise, cKO mice also displayed motor neuron degeneration with abnormal architecture of NMJ. Specifically, the cKO mice revealed reduced motor neuron number with small neuronal size in lumbar spinal cord as well as denervating change, small motor endplates, and decreased myonuclei number at NMJ in skeletal muscles. To explore the mechanisms, we screened various muscle‐derived factors and found that myogenin is a potential candidate that myogenin expression was lower in skeletal muscles of cKO mice than wild‐type mice. Because NRIP and myogenin were colocalized around acetylcholine receptors at NMJ, we extracted RNA from synaptic and extrasynaptic regions of muscles using laser capture microdissection and showed that myogenin expression was especially lower at synaptic region in cKO than wild‐type mice. Notably, overexpression of myogenin using intramuscular adenovirus encoding myogenin treatment rescued abnormal NMJ architecture and preserved motor neuron death in cKO mice.ConclusionsIn summary, we demonstrated that deprivation of NRIP decreases myogenin expression at NMJ, possibly leading to abnormal NMJ formation, denervation of acetylcholine receptor, and subsequent loss of spinal motor neuron. Overexpression of myogenin in cKO mice can partially rescue abnormal NMJ architecture and motor neuron death. Therefore, muscular NRIP is a novel trophic factor supporting spinal motor neuron via stabilization of NMJ by myogenin expression.

show abstract

Section: Discussionsupporting

confidence: 82%

Muscle‐restricted nuclear receptor interaction protein knockout causes motor neuron degeneration through down‐regulation of myogenin at the neuromuscular junction

Chen

Tsai

Liao

et al. 2018

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…We tested the antiviral activity of PEG-CLS using lentivirus (LV, envelope protein: vesicular stomatitis virus G protein (VSV-G)), adenovirus (AdV), adeno-associated virus 2 (AAV), and pseudotype particle for SARS-CoV-2 (SARS-CoV-2-PP) using the spike of SARS-CoV-2 as an envelope protein in the lentivirus. , Two genes, ACE2 and TMPRSS2 that are a receptor for spike and a protease to activate spike and are required for SARS-CoV-2 infection, respectively, were transfected to HEK293T cells prior to SARS-CoV2-PP infection, as otherwise the infection of SARS-CoV-2-PP to this cell line was not detectable (data not shown) . The estimated physical dimensions of PEGs, viruses, and receptors for viruses are depicted in Figure B–D. ,− We infected these viruses to HEK293T cells that were dispersed in a solution and precoated with PEG-CLS, and PEG-CLS was kept in the solution during the infection to ensure persistent coating. After the removal of both PEG-CLS and viruses by washing, the infected cells were cultured for 2 additional days and transduced genes from the viruses were analyzed.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Activity of Cell Membrane-Bound Amphiphilic Polymers

Kaizuka

Machida

2023

Langmuir

View full text Add to dashboard Cite

We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to protect the epithelium from viruses. When these polymers are applied to the epithelium, they localize on the apical surface due to the tight junction barriers, resulting in surface-only coating. Therefore, these polymers can prevent the entry of viruses into cells of the epithelium with minimal disturbance to lateral cell−cell interactions and organizations. ■ EXPERIMENTAL SECTIONSPlasmids, Viruses, and Cells. Plasmids pCAG-HIVgp and pCMV-VSV-G-RSV-Rev (obtained from Hiroyuki Miyoshi, Riken BRC, Japan) were used for packaging of lentiviruses. For SARS-CoV-2 pseudoparticles, the VSV-G gene in the pCMV-VSV-G-RSV-Rev was replaced with the spike gene (SARS-CoV-2, Wuhan-Hu-1, obtained from SinoBio, China). These plasmids were cotrasnfected to HEK293T cells with another plasmid, pLV-eGFP (obtained from Pantelis Tsoulfas) or pLenti CMV Puro LUC (obtained from Eric Campeau). Lentiviruses and SARS-CoV-2-PP are self-inactivating and not able to replicate. Both lentivirus and SARS-CoV-2 PP viruses were collected from a supernatant medium and concentrated using a Lenti-X concentrator kit (Takara bio, Japan). Lenti-X p24 Rapid Titer Kit (Takara Bio) was used to measure the titer of collected viruses by ELISA (enzyme-linked immunosorbent assay). Plasmids of AAV GFP, pAdDeltaF6, and pAAV2/2 (obtained from Fred Gage, James M. Wilson, and Melina Fan, respectively) were cotrasnfected to HEK293T cells to produce adeno-associated viruses, which were collected from both the medium and supernatant of cell lysis. The adeno-associated virus was not replicated in HEK293T cells in our infection assays due to the absence of genes from the adenovirus that

show abstract

“…This is not feasible with current biotechnology, as large vectors cannot efficiently extravasate in most regions throughout the body after IV injection. Similarly, large vectors do not diffuse much when injected directly into parenchymal tissue 18 . It is true that extracellular matrix (ECM)-remodeling proteins can be injected with the vector to enhance its distribution throughout the tumor, but automatic replication and intercellular spreading based on mutation detection would still be helpful to minimize the number of injections required to make complete coverage a more likely outcome.…”

mentioning

confidence: 99%

Promoting Oncolytic Vector Replication with Switches that Detect Ubiquitous Mutations

Renteln¹

2024

CCTR

View full text Add to dashboard Cite

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.

show abstract

A reduction in the human adenovirus virion size through use of a shortened fibre protein does not enhance muscle transduction following systemic or localised delivery in mice

Cited by 6 publications

References 75 publications

Muscle‐restricted nuclear receptor interaction protein knockout causes motor neuron degeneration through down‐regulation of myogenin at the neuromuscular junction

Muscle‐restricted nuclear receptor interaction protein knockout causes motor neuron degeneration through down‐regulation of myogenin at the neuromuscular junction

Antiviral Activity of Cell Membrane-Bound Amphiphilic Polymers

Promoting Oncolytic Vector Replication with Switches that Detect Ubiquitous Mutations

Contact Info

Product

Resources

About