Scientists are developing a new generation of non-integrating viral vectors capable of nuclear persistence through serial mitotic cycles and stable under selection to offset the comparatively lower transduction rates. Here, the authors review the competing approaches to develop such non-integrating lentiviral (NILV) episome vectors that faithfully replicate in stem cells.
Here, the authors used a Non Integrating Lentiviral Vector (NILV) to express Igf-1 under the control of the synapsin promoter which is neuron specific. Their investigations of neurotrophic effects on primary rat neuronal cultures demonstrated that neurons transduced with the NILV Igf-1 vectors had complete protection upon with drawal of exogenous trophic support. However, striatal transduction of such vectors into 6-OHDA-lesionedrats provided neither protection of dopaminergic substantia nigra neurons nor improvement of animal behavior.
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In this study, the scientists established a methodology allowing an adjustment of expression windows to a period of choice, even for the simultaneous expression of multiple transgenes, based on the repeated administration of lentiviral and gammaretroviral vectors.
the authors developed an integration-deficient lentiviral vector termed ID-VP02 that is designed to deliver antigen-encoding nucleic acids selectively to human DCs in vivo. ID-VP02 utilizes a genetically and glycobiologically engineered Sindbis virus glycoprotein to target human DCs through the C-type lectin DC-SIGN (CD209) and also binds to the homologue murine receptor SIGNR1.
The authors compared six HIV vectors carrying different integrases, either wild type or with different mutations shown to modify integrase enzymatic activity, oligomerization, or interaction with key cellular cofactor of HIV DNA integration as LEDGF/p75 or TNPO3. They report that an integrase carrying the D167H substitution improves vector transduction efficiency and integration in both HEK-293T and primary CD34+ cells.
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Promising results about the use of Non Integrating Lentiviral Vectors for vaccination.
GEG-tech offers the largest range of Non Integrating Lentiviral Vectors. Different integrase mutations are available and you have the possibility to select the NILVs the most adapted for your research thanks to our "set of vectors".
In this study, the authors designed a non integrating lentiviral vector which expresses diphtheria toxin A under the control of the Survivin promoter which is dramatically activated in cancer tissues and cells. Their results suggest that the IDLV system that we generated possesses therapeutic potential in cancers in vitro and in vivo.
Thanks to Non Integrating Lentiviral Vectors which express ZFN, the scientists demonstrated efficient targeted cleavage at the beta-globin locus with minimal off-target modification. By co-delivering a homologous donor template, high levels of gene modification were achieved in CD34+ hematopoietic stem and progenitor cells (HSPCs).
To optimize Zinc Finger Nuclease (ZFN) delivery from a single lentiviral vector (LV), the authors used a codon swapping strategy to both drastically disrupt sequence identity between ZFN monomers and to reduce sequence repeats within a monomer sequence. In this way, they observed a ZFN activity up to 7 fold increased compared to non optimized ZFN LV.
Furthermore, they reported for the first time successful ZFN-induced targeted DNA double-strand breaks in primary cells (hepatocytes) and in vivo (liver) after delivery of a single non integrating lentiviral vector encoding two ZFNs.
The lentiviral vector is a multifaceted tool. Indeed, different sort of vectors can be derived from the lentivirus HIV-1 , each with their own features. This video explain how work three of them.
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The authors used non-integrating lentivirus (NILV) for transient expression of ZFNs and pseudotyped the virus with HIV-envelope for targeted delivery to CD4+ T cells. Both activated and resting primary CD4+ T cells transduced with CCR5-ZFNs NILV showed resistance to HIV-1 infection in vitro.
GEG-tech offers a large choice in Non Integrating Lentiviral Vectors
The miniMAR variant of the human β-interferon S/MAR induces stable expression of non integrating lentiviral vector in dividing cells. Interesting element in gene transfer field!
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Scientists are developing a new generation of non-integrating viral vectors capable of nuclear persistence through serial mitotic cycles and stable under selection to offset the comparatively lower transduction rates. Here, the authors review the competing approaches to develop such non-integrating lentiviral (NILV) episome vectors that faithfully replicate in stem cells.