Resveratrol trimer enhances gene delivery to hematopoietic stem cells by reducing antiviral restriction at endosomes

Ozog, Stosh; Timberlake, Nina; Hermann, Kip; Garijo, Olivia; Haworth, Kevin G.; Shi, Guoli; Glinkerman, Christopher M.; Schefter, Lauren E; D'Souza, Saritha S.; Simpson, Elizabeth M.; Sghia-Hughes, Gabriella; Carillo, Raymond R.; Boger, Dale L.; Kiem, Hans–Peter; Slukvin, Igor I.; Ryu, Byoung Y.; Sorrentino, Brian P.; Adair, Jennifer E.; Snyder, Scott A.; Compton, Alex A.; Torbett, Bruce E.

doi:10.1182/blood.2019000040

Cited by 27 publications

(21 citation statements)

References 85 publications

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“…Recently, scientists have discovered that caraphenol A, a trimer of resveratrol, plays a unique role in gene therapy, which has brought resveratrol back into the spotlight. Torbett et al found that caraphenol A safely enhanced the gene delivery efficiency from LVs (lentiviral vector) to the HSC (hematopoietic stem cell), also reducing the transmembrane protein-mediated restriction to making it easier for vectors to pass through, which is a possible way to improve the therapeutic effect of gene therapy [19].…”

Section: Introductionmentioning

confidence: 99%

The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells

Liang

Zhu

et al. 2019

Toxins

119

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Resveratrol, a natural polyterpenoid, can scavenge reactive oxygen species in vivo to carry out the functions of antioxidation and antiaging. Resveratrol's anti-cancer capability has attracted widespread attention, but its molecular mechanism has not been systematically explained. In this study, by comparing the activity of normal cell lines and cancer cell lines after treating with resveratrol, it was found that resveratrol has more significant cytotoxicity in cancer cell lines. Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a timeand concentration-dependent manner. A total of 330 significantly differential genes were identified through large-scale transcriptome sequencing, among which 103 genes were upregulated and 227 genes were downregulated. Transcriptome and qRT-PCR data proved that a large number of genes related to cell cycle were differentially expressed after the treatment of resveratrol. The changes of cell cycle phases at different time points after treating with resveratrol were further detected, and it was found that the cells were arrested in the S phase because of the percentage of cells in S phase increased and cells in G1/G0 phase decreased. In conclusion, resveratrol can inhibit the proliferation of 4T1 cancer cells by inhibiting cell cycle and inducing apoptosis. Key Contribution:Resveratrol exerts a more obvious toxic effect on cancer cells to induce apoptosis in a time-and dose-dependent manner. RNA-seq was used to overall explore potential mechanisms from a transcriptional level.

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Section: Introductionmentioning

confidence: 99%

The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells

Liang

Zhu

et al. 2019

Toxins

119

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“… 32 IFITM3 has been investigated most and was recently identified as the main target to improve gene transfer into hematopoietic stem cells through the use of resveratrol as transduction enhancer. 33 , 34 , 35 Although our data certainly support this strategy also for T lymphocytes, they also suggest that not only intracellular localization of IFITMs but also subtle changes in their overall expression levels may determine whether a particular T cell becomes properly transduced. 35 …”

Section: Discussionmentioning

confidence: 52%

Monitoring CAR T cell generation with a CD8-targeted lentiviral vector by single-cell transcriptomics

Charitidis

Adabi

Thalheimer

et al. 2021

Molecular Therapy - Methods & Clinical Development

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Quantifying gene expression in individual cells can substantially improve our understanding about complex genetically engineered cell products such as chimeric antigen receptor (CAR) T cells. Here we designed a single-cell RNA sequencing (scRNA-seq) approach to monitor the delivery of a CD19-CAR gene via lentiviral vectors (LVs), i.e., the conventional vesicular stomatitis virus (VSV)-LV and the CD8-targeted CD8-LV. LV-exposed human donor peripheral blood mononuclear cells (PBMCs) were evaluated for a panel of 400 immune response-related genes including LV-specific probes. The resulting data revealed a trimodal expression for the CAR and CD8A , demanding a careful distribution-based identification of CAR T cells and CD8+ lymphocytes in scRNA-seq analysis. The fraction of T cells expressing high CAR levels was in concordance with flow cytometry results. More than 97% of the cells hit by CD8-LV expressed the CD8A gene. Remarkably, the majority of the potential off-target cells were in fact on-target cells, resulting in a target cell selectivity of more than 99%. Beyond that, differential gene expression analysis revealed the upregulation of restriction factors in CAR -negative cells, thus explaining their protection from CAR gene transfer. In summary, we provide a workflow and subsetting approach for scRNA-seq enabling reliable distinction between transduced and untransduced cells during CAR T cell generation.

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“…The diarrhea index formula given below of the four groups are given: Resveratrol have many antiviral properties and used against the Rotavirus diarrhea and enterovirus [39], which cause the inflammation of the hearts of mice, which reduced the hearts ability to pump he blood normally and blocked the replication of enterovirus [40]. Therefore, we use he resveratrol against the Rotavirus, which is harmful for the piglets [41], which cause diarrhea and gastroenteritis in piglets and we know that resveratrol dry suspension could regulate the immune response and inhibit the diarrhea and other viral infection [42].…”

Section: Diarrhea Indexmentioning

confidence: 99%

A Review: Positive Outcome of Resveratrol Dry Suspension in Piglets against Rotavirus Infection

Sultan

Iqbal

Amjad

et al. 2021

IJPR

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Rota virus that cause diarrhea and other diseases in small infants is belonging to a virus family called Reoviridae with death rate of about more than 200000 annually. Although many vaccines are available for Rotavirus infection but still primary reason of death among infants. To prevent infection caused by this virus as diarrhea and other gastroenteritis in piglets we use a resveratrol, a natural phenol and a phytoalexin with a potential of strong antibiotic and antiviral, which has preventive and protecting outcome against Rotavirus infection in piglets. Pretreatment done and resveratrol dry suspension added to the adequate essential nutrient (basal diet) and the animal through oral route done Rotavirus and then know about the outcome of resveratrol dry suspension. Therefore, our main concern is to use the resveratrol dry suspension, which produced immunity in piglets against Rotavirus. It has positive outcome and reduced the diarrhea and other gastroenteritis. Therefore, the outcome of resveratrol dry suspension shows that it could be the best one to treat the diarrhea and other disease, which caused by this virus.

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Resveratrol trimer enhances gene delivery to hematopoietic stem cells by reducing antiviral restriction at endosomes

Abstract: Key Points The cyclic resveratrol trimer caraphenol A safely enhances lentiviral vector gene delivery to hematopoietic stem and progenitor cells. Caraphenol A decreases interferon-induced transmembrane protein-mediated restriction in an endosomal trafficking-dependent manner.

Cited by 27 publications

References 85 publications

The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells

The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells

Monitoring CAR T cell generation with a CD8-targeted lentiviral vector by single-cell transcriptomics

A Review: Positive Outcome of Resveratrol Dry Suspension in Piglets against Rotavirus Infection

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