Overview of Gene Delivery into Cells Using <scp>HSV</scp>‐1‐Based Vectors

Neve, Rachael L.; Lim, Filip

doi:10.1002/0471142301.ns0100s06

Cited by 17 publications

(19 citation statements)

References 44 publications

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“…However, it may be possible to adapt the transgene cassette design of the current study to other vector systems to allow the efficient construction of constructs that exceed lentivirus and AAV packaging limits with a wide variety of promoters. For example, the herpes simplex virus vector system can accommodate inserts up to ~150 kb 35 and can easily transduce dividing and post-mitotic cell types without eliciting an immunological response 36,37 .…”

Section: Discussionmentioning

confidence: 99%

CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype

et al. 2014

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Mutations in CEP290 are the most common cause of Leber congenital amaurosis (LCA), a severe inherited retinal degenerative disease for which there is currently no cure. Autosomal recessive CEP290-associated LCA is a good candidate for gene-replacement therapy, and cells derived from affected individuals give researchers the ability to study human disease and therapeutic gene correction in vitro. Here we report the development of lentiviral vectors carrying full-length CEP290 for the purpose of correcting the CEP290 disease-specific phenotype in human cells. A lentiviral vector containing CMV-driven human full-length CEP290 was constructed. Following transduction of patient-specific, iPSC-derived, photoreceptor precursor cells, rt-PCR analysis and western blotting revealed vector-derived expression. Because CEP290 is important in ciliogenesis, the ability of fibroblast cultures from CEP290-associated LCA patients to form cilia was investigated. In cultures derived from these patients, fewer cells formed cilia compared to unaffected controls. Cilia that were formed were shorter in patient derived cells than in cells from unaffected individuals. Importantly, lentiviral delivery of CEP290 rescued the ciliogenesis defect. The successful construction and viral transfer of full-length CEP290 brings us closer to the goal of providing gene- and cell- based therapies for patients affected with this common form of LCA.

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Section: Discussionmentioning

confidence: 99%

CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype

et al. 2014

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“…CBPDHAT or mCREB and/or EGFP were cloned into the HSV amplicon and packaged using a replication-defective helper virus as previously described Neve and Lim 2001). The viruses (HSV/CMV-CBPDHAT-IRES2-EGFP, HSV/CMV-EGFP, and HSV/mCREB-EGFP) were prepared by Dr. Rachael Neve (MIT, Viral Core Facility).…”

Section: Virusesmentioning

confidence: 99%

Prefrontal consolidation supports the attainment of fear memory accuracy

et al. 2014

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The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive.

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“…Newer-generation vectors have been developed to limit transsynaptic spread to a single synapse, eliminating the toxicity. These self-limiting vectors have also been used for traditional gene therapy studies (HSV-1, Goins et al 2014;Neve 2012) and monosynaptic tracing (rabies and pseudorabies; Arenkiel and Ehlers 2009).…”

Section: Viral Vector Use In Neurosciencementioning

confidence: 99%

Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology

Sizemore

Seeger-Armbruster

Hughes

et al. 2016

Journal of Neurophysiology

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Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients.

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Overview of Gene Delivery into Cells Using HSV‐1‐Based Vectors

Cited by 17 publications

References 44 publications

CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype

CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype

Prefrontal consolidation supports the attainment of fear memory accuracy

Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology

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