New Methods for Disease Modeling Using Lentiviral Vectors

Alfranca, Arántzazu; Campanero, Miguel R.; Redondo, Juan Miguel

doi:10.1016/j.molmed.2018.08.001

Cited by 24 publications

(12 citation statements)

References 78 publications

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“…8a). The shRNAencoding lentivirus also encoded green fluorescent protein (GFP) to facilitate assessment of transduction efficiency 48,49 . In vitro transduction of MFS VSMCs with control shRNA (shScr), shPrkg1-A, or shPrkg1-B lentivirus yielded similar GFP mRNA expression levels, and Prkg1 expression was specifically silenced by shPrkg1-A and shPrkg1-B lentiviruses (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

et al. 2021

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Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

et al. 2021

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“…However, the small payload for transgene up tõ 4.5-5 kb, low viral production efficiency and slow expression time of ≥3 weeks are the major limitations of AAV viruses. Lentivirus, which has relatively faster production, larger payload of up to~8-10 kb, shorterexpression time of~1-2 weeks, and long-lived expression of multiple months [65][66][67], offers a solution in compromise.…”

Section: Practical Solutionsmentioning

confidence: 99%

Genetically encoded sensors enable micro- and nano-scopic decoding of transmission in healthy and diseased brains

et al. 2020

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Neural communication orchestrates a variety of behaviors, yet despite impressive effort, delineating transmission properties of neuromodulatory communication remains a daunting task due to limitations of available monitoring tools. Recently developed genetically encoded neurotransmitter sensors, when combined with superresolution and deconvolution microscopic techniques, enable the first micro- and nano-scopic visualization of neuromodulatory transmission. Here we introduce this image analysis method by presenting its biophysical foundation, practical solutions, biological validation, and broad applicability. The presentation illustrates how the method resolves fundamental synaptic properties of neuromodulatory transmission, and the new data unveil unexpected fine control and precision of rodent and human neuromodulation. The findings raise the prospect of rapid advances in the understanding of neuromodulatory transmission essential for resolving the physiology or pathogenesis of various behaviors and diseases.

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“…Virus-based systems, such as the lentiviral vectors, have shown high transfection efficiency for gene transfer. 21,22 However, high risks of immunogenicity and off-target problems hindered its F I G U R E 1 Extracellular barriers to RNAi therapy. (A) Endonucleases degrade siRNA in circulation; (B) the mononuclear phagocytic system, in particular the macrophages of the major clearance organs (e.g., liver, lungs, and spleen), removes siRNA from circulation; (C) tissue penetration of siRNA is hindered by charge repulsion between the anionic siRNA and the plasma membrane of endothelial cells, as well as tight junctions in selective regions (e.g., the blood-brain barrier) that require transcellular or paracellular transport to reach the target tissue.…”

Section: Nanoparticles For Sirna Deliverymentioning

confidence: 99%

Nanoparticle‐mediated siRNA delivery systems for cancer therapy

Gao

Chen

Santos

2021

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The small interfering RNA (siRNA)-based therapeutics have raised great attention since the first RNA interference (RNAi)-derived drug, patisiran, was approved by the US Food and Drug Administration, which represented a landmark in the field of gene therapy. Given the properties of interfering diseaseassociated gene expression, RNAi machinery is regarded as an essential factor for preparing precise medicine. However, over the past few years, siRNA drugs are undergoing a period of clinical translation, in which the major hurdle is the limited efficient delivery strategies. Therefore, this mini-review mainly focuses on describing the state-of-the-art of the nanoscale platforms for delivering siRNA payloads, also addressing their applications in cancer therapy. Finally, the status of siRNA drugs under clinical trials is discussed, providing a comprehensive understanding on the field of oligonucleotide-mediated therapeutics.

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New Methods for Disease Modeling Using Lentiviral Vectors

Cited by 24 publications

References 78 publications

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

Genetically encoded sensors enable micro- and nano-scopic decoding of transmission in healthy and diseased brains

Nanoparticle‐mediated siRNA delivery systems for cancer therapy

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