Simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain

Liehl, Beate; Hlavatý, Juraj; Moldzio, Rudolf; Tonar, Zbyněk; Unger, Hermann; Salmons, Brian; Günzburg, Walter H.; Renner, Matthias

doi:10.1038/sj.gt.3302988

Cited by 20 publications

(13 citation statements)

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“…The three plasmid-encoded vector was generated by transfection of 293T cells with pViFCGdBH encoding for the marker gene eGFP, Sgpdelta2 encoding for gag and pol (SIVmac) [7,8] and pMD.G. Transfectants were incubated for 2 days in DMEM (Biochrom, Berlin, Germany) supplemented with 10% FCS.…”

Section: Generation Of Lentiviral Gene Transduction Vector Particlesmentioning

confidence: 99%

“…HIV-2 ROD A Denv-GFP (ROD A) [5] is a HIV-2-derived two plasmid system sharing several characteristics of the SIVsmm derived PBj DE EGFP vector (PBj) [6] with the exception that in ROD A nef is replaced by GFP whereas in PBj nef is still present, and GFP expression is controlled by a CMV promoter. The third vector analyzed in this study, SIVmac DE EGFP (SIVmac) [7,8], is a SIV-derived selfinactivating (SIN) three plasmid vector system. SIVmac contains a deletion of the U3 region of the 3 0 -LTR conferring the SIN property, whereas the rev-responsive element, the exons for rev and tat, as well as the cPPT/CTS sites are left intact.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Analysis of Transduced Primary Human Dendritic Cells Generated by the Use of Three Different Lentiviral Vector Systems

et al. 2010

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Lentiviral gene transfer vectors are suitable for genetically modifying non-cycling primary human cells. In this study, we analyzed transduced human dendritic cells (DC) generated by the use of three different GFP-encoding lentiviral vectors, HIV-2 ROD A Δenv-GFP (ROD A), SIVsmm PBj ΔE EGFP (PBj), and SIVmac ΔE EGFP (SIVmac). CD14+ monocytes were isolated from buffy coat, transduced, and differentiated to immature and mature DC. Cytofluometric analysis of DC revealed high transduction efficiencies at MOI 1 for simian immunodeficiency virus (SIV)-derived vectors PBj and SIVmac ranging between 80-90 and 70-90%, respectively. In contrast, transduction with ROD A resulted only in approximately 30%-positive DC at the same MOI. Of note, none of the analyzed vectors affected expression of maturation and/or activation markers. Moreover, transduction with PBj or SIVmac did not induce significant cytokine responses whereas ROD A transduction stimulated weak interferon-alpha responses. SIVmac transduced DC showed normal phagocytosis of antigen and normal allo T cell stimulatory capacity when compared with untreated DC. Thus, the SIVmac lentiviral transduction vector is suitable for efficient genetic modification of human DC without affecting phenotype or function and thus qualifies this vector as a versatile tool for use in basic research.

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Section: Generation Of Lentiviral Gene Transduction Vector Particlesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Transduced Primary Human Dendritic Cells Generated by the Use of Three Different Lentiviral Vector Systems

et al. 2010

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“…Among lentiviruses, human immunodeficiency virus (HIV) 1‐based vectors were the first to be developed and were most widely used in scientific research (Picanco‐Castro et al, ). Besides, there are feline immunodeficiency virus (FIV; Da Silva et al, ), simian immunodeficiency virus (SIV; Liehl et al, ), bovine immunodeficiency virus (BIV; Berkowitz et al, ), equine infectious anemia virus (EIAV; Pezet et al, ), caprine arthritis‐encephalitis virus (Mselli‐Lakhal et al, ) and so on. Researchers' opinion on which virus is more safe and efficient is inconsistent.…”

Section: Structure Of Lentiviral and Aav Vectorsmentioning

confidence: 99%

Lentiviral Vectors and Adeno‐Associated Virus Vectors: Useful Tools for Gene Transfer in Pain Research

Zheng

Wang

Bai

et al. 2018

The Anatomical Record

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Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research. In this review, we thoroughly outline the structure, category, advantages and disadvantages and the delivery methods of lentiviral and AAV vectors. The methods through which lentiviral and AAV vectors are delivered to targeted sites are closely related with the sites, level and period of transgene expression. Focus is placed on the various delivery methods applied to deliver vectors to spinal cord and dorsal root ganglion both of which play important roles in primary nociception. Our goal is to provide insight into the features of these two viral vectors and which administration approach can be chosen for different pain researches. Anat Rec,

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“…While the transduction efficiency with viral vectors in general is largely dependent on titre, further limitations of the ability to transduce cells are imposed, in vivo mainly through the restricted diffusion of lentivector particles around the injection site within the extracellular matrix of the brain [2], and in vitro, especially for lower multiplicities of infection (MOIs), through an as yet poorly understood restriction. In many studies this is circumvented by transducing at early time points or simultaneously with seeding cells [3], [4], [5],[6],[7],[8],[9],[10]. In general transduction efficiency is thought to decrease with increasing age of the neuronal culture (days in vitro ; DIV) but few groups have systematically investigated this.…”

Section: Introductionmentioning

confidence: 99%

Tackling Obstacles for Gene Therapy Targeting Neurons: Disrupting Perineural Nets with Hyaluronidase Improves Transduction

2013

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Gene therapy has been proposed for many diseases in the nervous system. In most cases for successful treatment, therapeutic vectors must be able to transduce mature neurons. However, both in vivo, and in vitro, where preliminary characterisation of viral particles takes place, transduction of neurons is typically inefficient. One possible explanation is that the extracellular matrix (ECM), forming dense perineural nets (PNNs) around neurons, physically blocks access to the cell surface. We asked whether co-administration of lentiviral vectors with an enzyme that disrupts the ECM could improve transduction efficiency. Using hyaluronidase, an enzyme which degrades hyaluronic acid, a high molecular weight molecule of the ECM with mainly a scaffolding function, we show that in vitro in mixed primary cortical cultures, and also in vivo in rat cortex, hyaluronidase co-administration increased the percentage of transduced mature, NeuN-positive neurons. Moreover, hyaluronidase was effective at doses that showed no toxicity in vitro based on propidium iodide staining of treated cultures. Our data suggest that limited efficacy of neuronal transduction is partly due to PNNs surrounding neurons, and further that co-applying hyaluronidase may benefit applications where efficient transduction of neurons in vitro or in vivo is required.

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Simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain

Cited by 20 publications

References 58 publications

Comparative Analysis of Transduced Primary Human Dendritic Cells Generated by the Use of Three Different Lentiviral Vector Systems

Comparative Analysis of Transduced Primary Human Dendritic Cells Generated by the Use of Three Different Lentiviral Vector Systems

Lentiviral Vectors and Adeno‐Associated Virus Vectors: Useful Tools for Gene Transfer in Pain Research

Tackling Obstacles for Gene Therapy Targeting Neurons: Disrupting Perineural Nets with Hyaluronidase Improves Transduction

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