The Nobel Prize in Physiology or Medicine goes to John O'Keefe and May-Britt and Edvard Moser for work on cells that form a positioning system in the brain
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![]() The Nobel Prize in Physiology or Medicine goes to John O'Keefe and May-Britt and Edvard Moser for work on cells that form a positioning system in the brain No comment yet.
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![]() Presented herein are methods of generating an induced stem cell (iSC) from a somatic cell, by contacting the somatic cell with an induction factor that reprograms the somatic cell to generate an iSC. The induction factor can be a genetic construct or a fusion protein. Where the induction factor is a genetic construct, the construct bears one or more nucleotide sequences encoding one or more reprogramming elements selected from OCT4, SOX2, NANOG, and a Notch pathway molecule, or an active fragment or derivative thereof. The genetic construct can have a lentiviral or episomal vector backbone. The induction factor can also be a fusion protein, with the reprogramming element being a protein selected from OCT4, SOX2, NANOG, or a Notch pathway molecule, or an active fragment or derivative thereof. The fusion protein can be TAT protein or an active fragment or derivative thereof.
BigField GEG Tech's insight:
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BigField GEG Tech's insight:
Proof-of-principle of TALENs vectorization in RT-deficient lentiviral vectors. The authors achieved up to 58% knockout in CCR5+/293T reporter cells and up to 15% knockout of the natural TCR-locus in Jurkat cells.
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BigField GEG Tech's insight:
The authors developed a new lentiviral vector-based insertional mutagenesis screening to identify genes that confer resistance to clinically relevant targeted anti-cancer therapies. They successfully applied this approach to the identification of erlotinib resistance genes in pancreatic cancer, thus showing the intrinsic versatility of the approach.
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BigField GEG Tech's insight:
The authors demonstrate that, in vivo,, lentiviral vectors allow stable expression of shGFAP and shVIM which leads to a strong reduction of astrogliosis, improves functional motor recovery, and promotes axonal regrowth and sprouting of spared axons. This study thus examplifies how the nonneuronal environment might be a major target within the lesioned central nervous system to promote axonal regeneration (and sprouting) and validates the use of lentiviral-mediated RNAi in spinal cord injury
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BigField GEG Tech's insight:
The authors developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method. Each sgRNA is efficiently expressed and can mediate multiplex gene editing and sustained transcriptional activation in immortalized and primary human cells. This delivery system will be significant to enabling the potential of CRISPR/Cas9-based multiplex genome engineering in diverse cell types.
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BigField GEG Tech's insight:
The authors investigated the effects of overexpressed Sonic Hedgehog (SH) in a PD model rat. In this way, they use a lentiviral vector administered by stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. They found that overexpressed SH attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired.
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BigField GEG Tech's insight:
BigField GEG-tech.com's insight: The authors used a lentiviral vector to increase CRF expression site specifically in the amygdala of pre-weaning (postnatal day 12) female rats. In this way, they show that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.
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BigField GEG Tech's insight:
In this chapter, authors describe an approach to generate genetically modified resting B cells with lentiviral vectors using a protocol that is rapid, simple, and neither requires nor induces activation of B cells.
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BigField GEG Tech's insight:
The authors demonstrate that retrovirus-mediated protein transfer (RPT), retrovirus-mediated mRNA transfer (RMT), and retrovirus-mediated episome transfer (RET) represent powerful methodologies for transient protein delivery or protein expression. In these ways, the expression of ZFN induced gene disruption frequencies of up to 15% were achieved with RPT and RMT, and >50% gene knockout after RET
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![]() This introduction video shows how the choice of every vector element can modify the lentiviral vector's activity.
BigField GEG Tech's curator insight,
September 30, 2014 6:21 AM
Video which explains the influence of promoter, integrase or envelope on the activity of lentiviral vectors. The goal is to design the best vector according to the experimental needs.
![]() PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
BigField GEG Tech's insight:
The authors engineered rat MSCs with lentiviral vectors to either overexpress or knockdown microRNA-377 to investigate whether this microRNA regulated Mesenchymal-stem-cells (MSC)-induced myocardial angiogenesis. Results indicate that hypoxia-responsive microRNA-377 directly targets VEGF in MSCs, and knockdown of endogenous microRNA-377 promotes MSC-induced angiogenesis in the infarcted myocardium. Thus this microRNA may serve as a novel therapeutic target for stem cell-based treatment of ischemic heart disease.
http://geg-tech.com/rna-interference.html
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BigField GEG Tech's insight:
The authors inactivated specifically Gpr88 and D2 expression, tanks to lentiviral vectors mediated microRNA silencing strategy.The inactivation of D2 did not modify the locomotor response to Amph or the cognitive deficits induced by PCP, whereas the silencing of Gpr88 inhibited the Amph-induced hyperlocomotion and reduced the impairment of social novelty discrimination elicited by neonatal exposure to phencyclidine .
GEG-tech offers to vectorize in lentiviral system your own shRNA sequences
![]() PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
BigField GEG Tech's insight:
The authors showed that an intramuscular administration of IDLV followed by protein boosts using the sublingual route induced strong, persistent and complementary systemic and mucosal immune responses, and represents an appealing prime-boost strategy for immunization including IDLV as a delivery system.
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The authors demonstrated that after 6 months of overexpressing GDNF, 10-month-old 3xTg-AD mice showed preserved learning and memory. GDNF therapy did not significantly reduce amyloid and tau pathology, but rather, induced a potent upregulation of brain-derived neurotrophic factor that may act in concert with GDNF to protect neurons from atrophy and degeneration.
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![]() Long term therapeutic and reporter gene expression in lentiviral vector treated cystic fibrosis mice
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The authors treated CF mouse nasal airways with a Lentiviral Vector CFTR after pre-treatment with lysophosphatidylcholine. They observed CFTR gene expression lasting at least 12 months with an improvement of the survival of CF knockout mice treated with the LV CFTR.
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BigField GEG Tech's insight:
The authors show that lentiviral vectors can transduce efficiently cartilage cells (more than 85% of transduction rate) to further inhibit the expression of the Urokinase-type plasminogen activator gene (uPA) efficiently and steadily. Thus, the results provide the foundation for further research on the role of uPA in the pathogenesis of osteoarthritis.
http://geg-tech.com/rna-interference.html
![]() PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
BigField GEG Tech's insight:
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BigField GEG Tech's insight:
The authors used a shRNA lentiviral vector to silencing the CXCR7 gene. In this manner, they demonstrated that silencing of the CXCR7 gene represses the development of human colorectal cancer cells (CRC) through ERK and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of CRC.
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BigField GEG Tech's insight:
The authors design a minimally invasive TBX18 gene transfer strategy which creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model.
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BigField GEG Tech's insight:
The authors compare the efficiency of Integrase-Defective Lentiviral Vectors (IDLV) and Wilde Type Lentiviral Vectors (WTLV) to express CRAG in the taxia type 3 mouse model. They show 1 year after stereotaxic injections a drastic reduction of mutant aggregates in Purkinje cells with the two type of vectors. Considering that IDLVs reduce the risk of insertional mutagenesis, these results suggest that IDLVs are potentially effective for gene therapy whilst being safer than WTLV.
http://geg-tech.com/products/vectors.html?gamme=Lenti-ONE%E2%84%A2+Epi
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BigField GEG Tech's insight:
BigField GEG-tech.com's insight: Authers investigate the in vivo effect of FGF-2 overexpression on axonal regeneration after nerve injury. They transduced Schwann cells with LV-FGF2 which were grafted to repair the resected rat sciatic nerve. Electrophysiological tests conducted for up to 2 months after injury revealed accelerated and more marked reinnervation of hindlimb muscles in the animals treated with LV-FGF2, with an increase in the number of motor and sensory neurons that reached the distal tibial nerve at the end of follow-up.
http://geg-tech.com/products/vectors.html?applications=Neurology%2C+ophthalmology
BigField GEG Tech's curator insight,
July 9, 2014 10:51 AM
Authers investigate the in vivo effect of FGF-2 overexpression on axonal regeneration after nerve injury. They transduced Schwann cells with LV-FGF2 which were grafted to repair the resected rat sciatic nerve. Electrophysiological tests conducted for up to 2 months after injury revealed accelerated and more marked reinnervation of hindlimb muscles in the animals treated with LV-FGF2, with an increase in the number of motor and sensory neurons that reached the distal tibial nerve at the end of follow-up.
http://geg-tech.com/products/vectors.html?applications=Neurology%2C+ophthalmology
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