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

Abstract:

:Therapeutic gene delivery to hematopoietic stem cells (HSCs) holds great potential as a life-saving treatment of monogenic, oncologic, and infectious diseases. However, clinical gene therapy is severely limited by intrinsic HSC resistance to modification with lentiviral vectors (LVs), thus requiring high doses or repeat LV administration to achieve therapeutic gene correction. Here we show that temporary coapplication of the cyclic resveratrol trimer caraphenol A enhances LV gene delivery efficiency to human and nonhuman primate hematopoietic stem and progenitor cells with integrating and nonintegrating LVs. Although significant ex vivo, this effect was most dramatically observed in human lineages derived from HSCs transplanted into immunodeficient mice. We further show that caraphenol A relieves restriction of LV transduction by altering the levels of interferon-induced transmembrane (IFITM) proteins IFITM2 and IFITM3 and their association with late endosomes, thus augmenting LV core endosomal escape. Caraphenol A-mediated IFITM downregulation did not alter the LV integration pattern or bias lineage differentiation. Taken together, these findings compellingly demonstrate that the pharmacologic modification of intrinsic immune restriction factors is a promising and nontoxic approach for improving LV-mediated gene therapy.

journal_name

Blood

journal_title

Blood

authors

Ozog S,Timberlake ND,Hermann K,Garijo O,Haworth KG,Shi G,Glinkerman CM,Schefter LE,D'Souza S,Simpson E,Sghia-Hughes G,Carillo RR,Boger DL,Kiem HP,Slukvin I,Ryu BY,Sorrentino BP,Adair JE,Snyder SA,Compton AA,Torbet

doi

10.1182/blood.2019000040

subject

Has Abstract

pub_date

2019-10-17 00:00:00

pages

1298-1311

issue

16

eissn

0006-4971

issn

1528-0020

pii

blood.2019000040

journal_volume

134

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}.

    abstract::PRKAR1A (R1A)-retinoic acid receptor-alpha (R1A-RARalpha) is the sixth RARalpha-containing fusion protein in acute promyelocytic leukemia (APL). Using the murine bone-marrow retroviral transduction/transformation assay, we showed that R1A-RARalpha fusion protein could transform bone-marrow progenitor/stem cells. In ge...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-07-232652

    authors: Qiu JJ,Lu X,Zeisig BB,Ma Z,Cai X,Chen S,Gronemeyer H,Tweardy DJ,So CW,Dong S

    更新日期:2010-01-21 00:00:00

  • Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia.

    abstract::Aberrant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML), and preclinical data for inhibition of Aurora kinases or Mdm2 are promising. However, it remains largely unknown whether the viability of cells exposed to Au...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-01-128611

    authors: Kojima K,Konopleva M,Tsao T,Nakakuma H,Andreeff M

    更新日期:2008-10-01 00:00:00

  • IL-13 production by donor T cells is prognostic of acute graft-versus-host disease following unrelated donor stem cell transplantation.

    abstract::Despite the success of human leukocyte antigen (HLA) typing in allogeneic stem cell transplantation (SCT) it is rare to find an unrelated donor that is perfectly matched, making identification of "permissive" mismatches of paramount importance. Here, we describe novel associations between donor T-cell cytokine product...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-01-0192

    authors: Jordan WJ,Brookes PA,Szydlo RM,Goldman JM,Lechler RI,Ritter MA

    更新日期:2004-01-15 00:00:00

  • ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency.

    abstract::Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanic...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2009-03-209221

    authors: Sauer AV,Mrak E,Hernandez RJ,Zacchi E,Cavani F,Casiraghi M,Grunebaum E,Roifman CM,Cervi MC,Ambrosi A,Carlucci F,Roncarolo MG,Villa A,Rubinacci A,Aiuti A

    更新日期:2009-10-08 00:00:00

  • Microsatellite instability and p53 mutations are associated with abnormal expression of the MSH2 gene in adult acute leukemia.

    abstract::Microsatellite instability (MSI) and p53 mutations have been reported to occur in a significant proportion of patients with therapy-related acute myeloid leukemia (AML). MSH2 is one of the genes involved in DNA mismatch repair to maintain fidelity of genomic replication, and defects of MSH2 are directly involved in MS...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zhu YM,Das-Gupta EP,Russell NH

    更新日期:1999-07-15 00:00:00

  • Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival.

    abstract::B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5(+) B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymp...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-02-0558

    authors: Novak AJ,Bram RJ,Kay NE,Jelinek DF

    更新日期:2002-10-15 00:00:00

  • Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction.

    abstract::Endothelial progenitor cell (EPC) mobilization has been reported following tissue damage, whereas no data are available regarding the mobilization of hematopoietic progenitor cells (HPCs). We performed the phenotypic and functional analysis of circulating CD34+ progenitor cells in patients with acute myocardial infarc...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-05-1831

    authors: Massa M,Rosti V,Ferrario M,Campanelli R,Ramajoli I,Rosso R,De Ferrari GM,Ferlini M,Goffredo L,Bertoletti A,Klersy C,Pecci A,Moratti R,Tavazzi L

    更新日期:2005-01-01 00:00:00

  • Gemtuzumab ozogamicin with or without interleukin 11 in patients 65 years of age or older with untreated acute myeloid leukemia and high-risk myelodysplastic syndrome: comparison with idarubicin plus continuous-infusion, high-dose cytosine arabinoside.

    abstract::We investigated treatment with gemtuzumab ozogamicin (GO) in 51 patients aged 65 years or older with newly diagnosed acute myeloid leukemia (AML), refectory anemia (RA) with excess of blasts in transformation, or RA with excess blasts. GO was given in doses of 9 mg/m(2) of body-surface area on days 1 and 8 or, therape...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1182/blood.v99.12.4343

    authors: Estey EH,Thall PF,Giles FJ,Wang XM,Cortes JE,Beran M,Pierce SA,Thomas DA,Kantarjian HM

    更新日期:2002-06-15 00:00:00

  • Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells.

    abstract::Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-kappaB activity by blocking proteasomal degradation of inhibitor of kappaBalpha (IkappaBalpha). Bortezomib in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-01-199604

    authors: Hideshima T,Ikeda H,Chauhan D,Okawa Y,Raje N,Podar K,Mitsiades C,Munshi NC,Richardson PG,Carrasco RD,Anderson KC

    更新日期:2009-07-30 00:00:00

  • Differential STAT3, STAT5, and NF-kappaB activation in human hematopoietic progenitors by endogenous interleukin-15: implications in the expression of functional molecules.

    abstract::Different forms of interleukin-15 (IL-15) have been identified and shown to elicit different transduction pathways whose impact on hematopoiesis is poorly understood. We demonstrated herein that hematopoietic CD34+ cells constitutively produced endogenous secreted IL-15 (ES-IL-15) that activated different transcriptio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-09-2760

    authors: Giron-Michel J,Caignard A,Fogli M,Brouty-Boyé D,Briard D,van Dijk M,Meazza R,Ferrini S,Lebousse-Kerdilès C,Clay D,Bompais H,Chouaib S,Péault B,Azzarone B

    更新日期:2003-07-01 00:00:00

  • Efficient infection, activation, and impairment of pDCs in the BM and peripheral lymphoid organs during early HIV-1 infection in humanized rag2⁻/⁻γ C⁻/⁻ mice in vivo.

    abstract::Although plasmacytoid dendritic cells (pDCs) are involved in HIV-1 pathogenesis, the precise mechanism of interaction between pDCs and HIV-1 in vivo is not clear. The conflicting reports in HIV-1-infected patients highlight the importance of studying the interaction between HIV-1 and pDCs in relevant in vivo models. T...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-01-331173

    authors: Zhang L,Jiang Q,Li G,Jeffrey J,Kovalev GI,Su L

    更新日期:2011-06-09 00:00:00

  • Langerhans cell deficiency in reticular dysgenesis.

    abstract::Reticular dysgenesis is a rare inherited immunodeficiency characterized by the lack of blood monocytes and neutrophils and low lymphocyte counts, contrasting with normal red blood cell counts and normal or decreased platelet counts. Whether dendritic cells or macrophages, both of which derive primarily from blood mono...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Emile JF,Geissmann F,Martin OC,Radford-Weiss I,Lepelletier Y,Heymer B,Espanol T,de Santes KB,Bertrand Y,Brousse N,Casanova JL,Fischer A

    更新日期:2000-07-01 00:00:00

  • Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia.

    abstract::Virtually all cases of childhood ALL have chromosomal abnormalities and half contain translocations, which are nearly equally divided between random and nonrandom rearrangements. Nonrandom chromosomal abnormalities have been correlated with leukemic cell lineage, the degree of cell differentiation, and the specific ge...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:

    authors: Pui CH,Crist WM,Look AT

    更新日期:1990-10-15 00:00:00

  • Ly6G ligation blocks recruitment of neutrophils via a β2-integrin-dependent mechanism.

    abstract::Ly6G is a glycosylphosphatidylinositol (GPI)-anchored protein of unknown function that is commonly targeted to induce experimental neutrophil depletion in mice. In the present study, we found that doses of anti-Ly6G Abs too low to produce sustained neutropenia remained capable of inhibiting experimental arthritis, lea...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-01-404046

    authors: Wang JX,Bair AM,King SL,Shnayder R,Huang YF,Shieh CC,Soberman RJ,Fuhlbrigge RC,Nigrovic PA

    更新日期:2012-08-16 00:00:00

  • Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia.

    abstract::Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired imatinib resistance in patients with chronic myeloid leukemia (CML). Here we examine predisposing factors underlying acquisition of KD mutations, evidence for acquisition of mutations before and during therapy, and whether the ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-03-066936

    authors: O'Hare T,Eide CA,Deininger MW

    更新日期:2007-10-01 00:00:00

  • Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype.

    abstract::We studied T-cell reconstitution in 31 primary T-cell-immunodeficient patients who had undergone hematopoietic stem-cell transplantation (HSCT) over 10 years previously. In 19 patients, there was no evidence of myeloid chimerism because little or no myeloablation had been performed. Given this context, we sought facto...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-07-029090

    authors: Cavazzana-Calvo M,Carlier F,Le Deist F,Morillon E,Taupin P,Gautier D,Radford-Weiss I,Caillat-Zucman S,Neven B,Blanche S,Cheynier R,Fischer A,Hacein-Bey-Abina S

    更新日期:2007-05-15 00:00:00

  • Direct quantitation of platelet-associated IgG by electroimmunoassay.

    abstract::An electroimmunoassay was applied to the quantitation of platelet-associated IgG (PAIgG). Protein solubilized by Triton X100 from washed platelets was electrophoresed at pH 5.0 in agarose gels containing carbamoylated rabbit anti-human IgG (pI approximately equal to 5.0). Because the rabbit antibody is immobilized und...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kunicki TJ,Koenig MB,Kristopeit SM,Aster RH

    更新日期:1982-07-01 00:00:00

  • Stimulation of neutrophil oxidative metabolism by the alternate pathway of complement activation: a mechanism for the spontaneous NBT test.

    abstract::The reduction of nitroblue tetrazolium dye by human neutrophils was measured in the presence of serum in which the complement system had been activated through the alternate pathway by interaction with inulin. Neutrophils incubated with serum inulin supernatants reduced the dye and showed a general increase in oxidati...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Strauss RG,Mauer AM,Asbrock T,Spitzer RE,Stitzel AE

    更新日期:1975-06-01 00:00:00

  • Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes.

    abstract::Rh blood group antigens of the D, C/c, and E/e series are carried by at least three red cell membrane polypeptides encoded by two highly related genes, RHD and RHCE. Homozygous individuals carrying the D--, Dc-, and DCw- gene complexes are characterized by a total or partial lack of expression of the RHCE-encoded anti...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chérif-Zahar B,Raynal V,D'Ambrosio AM,Cartron JP,Colin Y

    更新日期:1994-12-15 00:00:00

  • Five years of experience with hydroxyurea in children and young adults with sickle cell disease.

    abstract::The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.11.3628

    authors: Ferster A,Tahriri P,Vermylen C,Sturbois G,Corazza F,Fondu P,Devalck C,Dresse MF,Feremans W,Hunninck K,Toppet M,Philippet P,Van Geet C,Sariban E

    更新日期:2001-06-01 00:00:00

  • Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.

    abstract::Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4160

    authors: Lan Q,Zheng T,Rothman N,Zhang Y,Wang SS,Shen M,Berndt SI,Zahm SH,Holford TR,Leaderer B,Yeager M,Welch R,Boyle P,Zhang B,Zou K,Zhu Y,Chanock S

    更新日期:2006-05-15 00:00:00

  • Sickle cell and silent spleen.

    abstract::In this issue of Blood, in a first-rate example of collaboration between academia (University of California) and industry (Sangamo), Hoban et al show in situ gene correction of sickle cell anemia (SCA), a prototypical hemoglobinopathy. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2015-03-633933

    authors: Tolar J

    更新日期:2015-04-23 00:00:00

  • Lymphoid differentiation of the hematopoietic stem cell that reconstitutes total erythropoiesis of a genetically anemic W/Wv mouse.

    abstract::We investigated whether the stem cell that reconstitutes total erythropoiesis of a WBB6F1-W/Wv mouse differentiates into lymphoid lineage. The electrophoretic pattern of hemoglobin was used as a marker of the reconstitution; 3-phosphoglycerate kinase (PGK), an X chromosome-linked enzyme was used as a tool for estimati...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nakano T,Waki N,Asai H,Kitamura Y

    更新日期:1989-04-01 00:00:00

  • Treatment of non-obese diabetic (NOD)/Severe-combined immunodeficient mice (SCID) with flt3 ligand and interleukin-7 impairs the B-lineage commitment of repopulating cells after transplantation of human hematopoietic cells.

    abstract::Until recently, the identification of cellular factors that govern the developmental program of human stem cells has been difficult due to the absence of repopulation assays that detect human stem cells. The transplantation of human bone marrow (BM) or cord blood (CB) into non-obese diabetic (NOD)/severe-combined immu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kapp U,Bhatia M,Bonnet D,Murdoch B,Dick JE

    更新日期:1998-09-15 00:00:00

  • Activation of human platelets by the rabbit anticardiolipin antibodies.

    abstract::Affinity purified anticardiolipin antibodies (ACLA) raised in rabbits showed cross-reactivities with various negatively charged phospholipids as shown by both the solid phase enzyme-linked immunosorbent assay (ELISA) and inhibition studies. In ELISA, ACLA showed strong cross-reactivity to both sphingomyelin (SM) and p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lin YL,Wang CT

    更新日期:1992-12-15 00:00:00

  • Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies.

    abstract::We investigated the clinical activity of the farnesyl transferase inhibitor R115777 in 22 patients with chronic myelogenous leukemia (CML) in chronic, accelerated, or blastic phase and in 8 patients with myelofibrosis (MF) and 10 patients with multiple myeloma (MM). R115777 was administered at 600 mg orally twice dail...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2002-07-1973

    authors: Cortes J,Albitar M,Thomas D,Giles F,Kurzrock R,Thibault A,Rackoff W,Koller C,O'Brien S,Garcia-Manero G,Talpaz M,Kantarjian H

    更新日期:2003-03-01 00:00:00

  • Asparaginase unveils glutamine-addicted AML.

    abstract::In this issue of Blood, Willems et al describe the dependence of acute myeloid leukemia (AML) cells on glutamine for maintaining protein synthesis downstream of mammalian target of rapamycin (mTOR) and show that the enzyme asparaginase can be used to target this dependence. Using various AML cell lines, primary sample...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2013-09-526392

    authors: Samudio I,Konopleva M

    更新日期:2013-11-14 00:00:00

  • Retention of B-cell-specific monoclonal antibodies by human lymphoma cells.

    abstract::The rates of endocytosis, intracellular degradation, and cell-surface shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti-CD19), B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by B-lymphoma cells were compared by cellular radioimmunoassay, ultrastructural autoradiography, sodium ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Press OW,Howell-Clark J,Anderson S,Bernstein I

    更新日期:1994-03-01 00:00:00

  • Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder.

    abstract::Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by deplet...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Vie H,Chevalier S,Garand R,Moisan JP,Praloran V,Devilder MC,Moreau JF,Soulillou JP

    更新日期:1989-07-01 00:00:00

  • Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia.

    abstract::An attractive hypothesis is that in utero exposure of hematopoietic cells to oncogenic agents can induce molecular changes leading to overt acute lymphoblastic leukemia (ALL) in infants and perhaps older children as well. Although supported by studies of identical infant twins with concordant leukemia, and of nontwine...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yagi T,Hibi S,Tabata Y,Kuriyama K,Teramura T,Hashida T,Shimizu Y,Takimoto T,Todo S,Sawada T,Imashuku S

    更新日期:2000-07-01 00:00:00