Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

Kobayashi, Kenta; Inoue, Ken; Tanabe, Soshi; Kato, Shigeki; Kobayashi, Kazuto

doi:10.3389/fnana.2017.00065

Cited by 23 publications

(16 citation statements)

References 61 publications

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“…The following virus vectors were used: fusion glycoprotein Type E (FuG-E)tetracycline-responsive element (TRE)-enhanced green fluorescent protein (EGFP)-enhanced tetanus neurotoxin light chain (eTeNT) (titer, 2.2-2.4 ϫ 10 12 copies/ml), FuG-E-murine stem cell virus (MSCV)-Cre (titer, 6.5 ϫ 10 10 copies/ml), adeno-associated virus (AAV)-DJcytomegalovirus (CMV)-reverse tetracycline transactivator (rtTAV16) (titer, 5.8 -6.8 ϫ 10 10 copies/ml), and AAV-DJ-elongation factor 1-␣ (EF1␣)-DIO-hM4D(Gi)-mCherry (titer, 5.0 ϫ 10 9 copies/ml). The FuG-E-pseudotyped vector was modified from a previously reported an HIV Type 1 (HIV-1)-based vector to produce enhanced efficiency of retrograde gene delivery (Kato et al, 2014;Kobayashi et al, 2017). FuG-E-TRE-EGFP-eTeNT and AAV-DJ-CMV-rtTAV16, comprising the Tet-on system, were used to blockade the cortico-rubral tract.…”

Section: Methodsmentioning

confidence: 99%

Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats

et al. 2019

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Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss of function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, whereas selective cortico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH.

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Section: Methodsmentioning

confidence: 99%

Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats

et al. 2019

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“…Modulating virus reservoir is essential to prevent HSK from recurrence. Our study showed preliminary evidence of retrograde transportation of HELP from corneas to TG using VSV-G pseudotyping, however, enhanced retrograde delivery may be achieved by pseudotyping HELP with derivatives of rabies virus glycoprotein, which may further strengthen the efficacy of HELP in clinical studies 31,32 .…”

Section: Figurementioning

confidence: 68%

Intracorneal delivery of HSV-targeting CRISPR/Cas9 mRNA prevents herpetic stromal keratitis

Yin

Ling

Wang

et al. 2020

Preprint

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1Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current 2 treatments for HSV-1 do not eliminate the virus and are incapable of modulating the virus 3 reservoir. Here, we target HSV-1 genome directly using mRNA-carrying lentiviral particle 4 (mLP) that simultaneously delivers spCas9 mRNA and two viral genes-targeting gRNAs 5 (designated HSV-1-erasing lentiviral particles, HELP). We showed HELP efficiently blocked 6 HSV-1 replication in both acute and recurrent infection models, and prevented occurrence of 7 herpetic stromal keratitis (HSK). We further showed retrograde transportation of HELP from 8 corneas to trigeminal ganglia (TG) where HSV-1 established latency and found evidence of 9 HELP modulating herpes reservoir. Additionally, the potent antiviral activity of HELP was 10 also replicable in human-derived corneas. These results strongly support clinical development 11 of HELP as a new antiviral therapy and may accelerate mRNA-based CRISPR therapeutics. 12

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“…To achieve selective initial infection of VON neurons by the rabies virus, we used the neural pathway specific-tracing method (tracing the relationship between input and output, TRIO 26 ). We first injected a retrograde Cre-coding lentiviral vector (NeuRet-Cre 27 ) into the LH, and Cre-dependent AAV vectors encoding TVA-mCherry and rabies G into the VON. Two weeks after the injection, we injected the modified rabies virus (SAD-dG-EGFP+EnvA) into the VON (Fig.…”

Section: Resultsmentioning

confidence: 99%

GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice

Murata

Kinoshita

Fukazawa

et al. 2018

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37Olfaction guides goal-directed behaviours including feeding. To investigate how central 38 olfactory neural circuits control feeding behaviour in mice, we performed retrograde 39 tracing from the lateral hypothalamus (LH), an important feeding centre. We observed a 40 cluster of retrogradely labelled cells distributed in the posteroventral region of the 41 olfactory peduncle. Histochemical analyses revealed that a majority of these 42 retrogradely labelled projection neurons expressed glutamic acid decarboxylase 65/67 43 (GAD65/67), but not vesicular glutamate transporter 1 (VGluT1). We named this region 44 with GABAergic projection neurons the ventral olfactory nucleus (VON) to 45 discriminate it from the conventional olfactory peduncle. VON neurons were less 46 immunoreactive for DARPP-32, a striatal neuron marker, in comparison to those in the 47 olfactory tubercle and nucleus accumbens, which distinguished the VON from the 48 ventral striatum. Fluorescent labelling confirmed synaptic contacts between VON 49 neurons and olfactory bulb projection neurons. Rabies-virus-mediated trans-synaptic 50 labelling revealed that VON neurons received synaptic inputs from the olfactory bulb, 51 other olfactory cortices, horizontal limb of the diagonal band, and prefrontal cortex.52 Collectively, these results identified novel GABAergic projection neurons in the 53 olfactory cortex that can integrate olfactory sensory and top-down inputs and send 54 inhibitory output to the LH, which may contribute to forming odour-guided LH-related 55 behaviours. 56 57 4 / 30 58 The central olfactory system translates odour information into motivated behaviours, 59 including appetite-based food approach and eating behaviours 1 . Recent studies have 60 revealed neuronal circuit mechanisms by which odorants evoke specific behaviours, 61 such as fear responses to predator odours 2,3 and attractive responses to social odours 4 . 62 However, it is still unclear how the central olfactory neural circuits control 63 feeding-related behaviours in mammals. 64 Odorants activate olfactory sensory neurons and coded by activation of specific 65 combinations of glomeruli in the olfactory bulb (OB), the first relay centre of the central 66 olfactory system 5 . Mitral cells and tufted cells (M/TCs) are projection neurons in the 67 OB. They convey odour information to several areas in the olfactory cortex which is 68 composed of the anterior olfactory nucleus (AON), tenia tecta, dorsal peduncular cortex, 69 anterior piriform cortex (APC), olfactory tubercle (OT), posterior piriform cortex (PPC), 70cortical amygdaloid nuclei, and entorhinal cortex 6 . 71 We previously reported that c-fos activity increased in the anteromedial domain 72 of the OT when mice showed attractive responses to a learned odour cue that predicted 73 food 7 . The OT has indirect anatomical connections to the lateral hypothalamus (LH), an 74 important feeding centre 8,9 , via the ventral pallidum 10 . Knowledge of neural pathways 75 from the olfactory cortex to the LH is crucial ...

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Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

Cited by 23 publications

References 61 publications

Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats

Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats

Intracorneal delivery of HSV-targeting CRISPR/Cas9 mRNA prevents herpetic stromal keratitis

GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice

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