Membrane Fusion Mediated Targeted Cytosolic Drug Delivery Through scFv Engineered Sendai Viral Envelopes.

Abstract:

:Antibody targeted cytoplasmic delivery of drugs is difficult to achieve as antigen-antibody interaction results in the payload being directed to the endosomal compartment. However, Sendai viral envelopes can bring about cytoplasmic delivery due to F-protein mediated membrane fusion. In this study we have generated and fused a recombinant scFv directed to the onco-fetal antigen, the Placental isozyme of Alkaline Phosphatase (PAP) with the trans-membrane and part of the cytoplasmic domain of the Sendai F protein (F(TMC)). Reconstituted virosomes, having both the fusion protein as well as the native F-protein were able to specifically bind and deliver drugs to PAP expressing cells. About 75% of the delivery was cytoplasmic in nature. Hence, this immuno-virosome, which is devoid of the comparatively more toxic HN protein, has the novel ability to combine specific antibody mediated targeting with cytoplasmic delivery. The scFv ensured specific binding to PAP expressing cells, without cross reacting with the other isozymes of alkaline phosphatase. The advantages of cytoplasmic delivery would include reduced degradation and lowered immunogenicity of the payload and carrier. The ubiquitous expression of PAP on a variety of cancers like seminoma, choriocarcinoma, cervical and breast cancers also suggests its potential usefulness in a number of malignancies.

journal_name

Curr Mol Med

authors

Kumar M,Mani P,Pratheesh P,Chandra S,Jeyakkodi M,Chattopadhyay P,Sarkar DP,Sinha S

doi

10.2174/1566524015666150505155949

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

386-400

issue

4

eissn

1566-5240

issn

1875-5666

pii

CMM-EPUB-67045

journal_volume

15

pub_type

杂志文章
  • Molecular Determinants of Colon Cancer Susceptibility in the East and West.

    abstract::The currently available knowledge of factors that dictate the development and progression as well as the clinical outcome of colorectal cancers (CRC) is mainly derived from Western countries. Considerable number of publications document different incidence rates and contrasting clinical features of CRC in various grou...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524017666170220094705

    authors: Abdel-Rahman WM,Faris ME,Peltomaki P

    更新日期:2017-01-01 00:00:00

  • Impact of Axis of GHRH and GHRH Receptor on Cell Viability and Apoptosis of the Placental Choriocarcinoma Cell Line.

    abstract::Although GHRH and GHRH-R are recognized as key factors in placental development, little is known about the mechanism(s) of the regulation in trophoblastic cells during placental development. The objective of this study is to determine the potential relationship between the expression levels of GHRH-R and the placental...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524016666160225154040

    authors: Liu AX,Zhang D,Zhu YM,Gao HJ,Jiang JY,Hu XL,Lv PP,Leung PC,Huang HF

    更新日期:2016-01-01 00:00:00

  • Nanotechnology as an adjunct tool for transplanting engineered cells and tissues.

    abstract::Laboratory and clinical studies have provided evidence of feasibility, safety and efficacy of cell transplantation to treat a wide variety of diseases characterized by tissue and cell dysfunction ranging from diabetes to spinal cord injury. However, major hurdles remain and limit pursuing large clinical trials, includ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652407782564381

    authors: Borlongan CV,Masuda T,Walker TA,Maki M,Hara K,Yasuhara T,Matsukawa N,Emerich DF

    更新日期:2007-11-01 00:00:00

  • VEGFR1 Signaling Regulates IL-4-Mediated Arginase 1 Expression in Macrophages.

    abstract:BACKGROUND:Macrophages undergo polarization or activation in response to environmental stimuli, an essential process for proper immune response. Meanwhile, excessive activation of macrophages causes autoimmune diseases. It is therefore crucial to prevent over-activation of macrophage in order to maintain the proper imm...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524017666171106114537

    authors: Zou Y,Chen Q,Ye Z,Li X,Ju R

    更新日期:2017-12-07 00:00:00

  • Suppression of NF-κB activation by gentian violet promotes osteoblastogenesis and suppresses osteoclastogenesis.

    abstract::Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures ar...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666140724104842

    authors: Yamaguchi M,Vikulina T,Arbiser JL,Weitzmann MN

    更新日期:2014-01-01 00:00:00

  • Therapeutic hypothermia as a neuroprotective strategy in neonatal hypoxic-ischemic brain injury and traumatic brain injury.

    abstract::Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated....

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652412803833517

    authors: Ma H,Sinha B,Pandya RS,Lin N,Popp AJ,Li J,Yao J,Wang X

    更新日期:2012-12-01 00:00:00

  • Plasma membrane electron transport: a new target for cancer drug development.

    abstract::The view that mitochondrial electron transport is the only site of aerobic respiration and the primary bioenergetic pathway in mammalian cells is well established in the literature. Although this paradigm is widely accepted for most tissues, the situation is less clear for proliferating cells. Increasing evidence indi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652406779010777

    authors: Herst PM,Berridge MV

    更新日期:2006-12-01 00:00:00

  • p53 peptide prevents LITAF-induced TNF-alpha-mediated mouse lung lesions and endotoxic shock.

    abstract::Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/156652411796268731

    authors: Tang X,O'Reilly A,Asano M,Merrill JC,Yokoyama KK,Amar S

    更新日期:2011-08-01 00:00:00

  • Protective antifungal yeast killer toxin-like antibodies.

    abstract::After several years of controversy, antibodies (Abs) are now believed to play an important role in the protection against fungal infections. Among them, recent data are strongly supporting the relevance of protective yeast killer toxin-like Abs ("antibiobodies", KT-Abs), which are able to exert a direct microbicidal a...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524054022558

    authors: Magliani W,Conti S,Frazzi R,Ravanetti L,Maffei DL,Polonelli L

    更新日期:2005-06-01 00:00:00

  • Hypercoagulability in sickle cell disease and beta-thalassemia.

    abstract::Sickle cell disease (SCD) and beta-thalassemia (also referred to as beta-thalassemia) are common hereditary hemoglobinopathies with differing pathophysiologies and clinical courses. However, patients with both diseases exhibit increased platelet and coagulation activation, as well as decreased levels of natural antico...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408786241366

    authors: Singer ST,Ataga KI

    更新日期:2008-11-01 00:00:00

  • A review of studies on targeting interleukin 4 receptor for central nervous system malignancy.

    abstract::Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652409788970661

    authors: Puri S,Puri S,Mahapatra AK,Hussain E,Sarkar C,Sinha S,Joshi BH

    更新日期:2009-08-01 00:00:00

  • The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress.

    abstract::Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Respo...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524016666160523143937

    authors: Rozpedek W,Pytel D,Mucha B,Leszczynska H,Diehl JA,Majsterek I

    更新日期:2016-01-01 00:00:00

  • Ursodeoxycholic Acid (UDCA) Promotes Lactate Metabolism in Mouse Hepatocytes through Cholic Acid (CA) - Farnesoid X Receptor (FXR) Pathway.

    abstract:BACKGROUND:Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism. METHOD:In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM ursode...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524020666200123161340

    authors: Wang L,He HW,Zhou X,Long Y

    更新日期:2020-01-01 00:00:00

  • Clinical laboratory testing in human medicine based on the detection of glycoconjugates.

    abstract::The purpose of this review is to provide a concise overview of developments over the last 15 years in the field of laboratory tests in human medicine that are based on the detection of alterations in the glycan part of glycoconjugates. We show how glycosylation-based diagnostic testing is widespread in the current cli...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652407780831629

    authors: Schulz BL,Laroy W,Callewaert N

    更新日期:2007-06-01 00:00:00

  • Effects of Morphine on Interstitial Cells of Cajal in Rabbit Colon and Small Intestinal Transit: An Experimental Study.

    abstract:OBJECTIVE:This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. METHODS:Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524019666191023112837

    authors: Yang H,Jin XJ,Luo H,Li YH

    更新日期:2020-01-01 00:00:00

  • RAN GTPase as a target for cancer therapy: Ran binding proteins.

    abstract::The identification of a relevant effector of Ran GTPase (Ran) signaling and its pathways could provide a novel approach to cancer therapeutics. With recent research highlighting the significant relationship between Ran expression and the occurrence and progression of cancer, the development of a small molecule compoun...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411797536688

    authors: Doherty KJ,McKay C,Chan KK,El-Tanani MK

    更新日期:2011-11-01 00:00:00

  • Recognition of classical and heavy chain forms of HLA-B27 by leukocyte receptors.

    abstract::As an MHC class I protein, the disease association of HLA-B27 with inflammatory arthritis has been widely assumed to imply a role for the T cell antigen receptor (TCR) in disease. However, in addition to their classical antigen-presenting role, HLA class I proteins are recognised by members of the killer immunoglobuli...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524043479329

    authors: Allen RL,Trowsdale J

    更新日期:2004-02-01 00:00:00

  • Orexigenic/anorexigenic signals in bulimia nervosa.

    abstract::Bulimia nervosa (BN) and Anorexia Nervosa (AN) are currently classified as eating disorders (ED). Both disorders are the product of complex interaction between physiological and psychological and social processes; they are characterized by abnormal eating behavior. However, patients with BN differ from AN in their nut...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033479762

    authors: Takimoto Y,Inui A,Kumano H,Kuboki T

    更新日期:2003-06-01 00:00:00

  • The study of HLA class II and autoimmune diabetes.

    abstract::Many autoimmune diseases have genetic associations with the Major Histocompatibility Complex (MHC) class II loci. Susceptibility to Type 1 diabetes mellitus (TIDM) is particularly associated with Human Leucocyte Antigen (HLA) DR3, 4 and associated DQ2, 8 alleles and this is well documented in genetic association studi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033361591

    authors: Wong FS,Wen L

    更新日期:2003-02-01 00:00:00

  • Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    abstract::Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biologic...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524011313050010

    authors: Shtrichman R,Germanguz I,Itskovitz-Eldor J

    更新日期:2013-06-01 00:00:00

  • New Horizons in the Etiopathogenesis and Non-Invasive Diagnosis of Endometriosis.

    abstract::Endometriosis is one of the most common gynecological inflammatory diseases, occurring in adolescents and women in the reproductive age group and leading to infertility. The precise etiopathogenesis of endometriosis is unknown, but several theories concerning the phenomena involved in its development have been propose...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524015666150921105218

    authors: Zubrzycka A,Zubrzycki M,Janecka A,Zubrzycka M

    更新日期:2015-01-01 00:00:00

  • Ipsilateral hippocampal proteomics reveals mitochondrial antioxidative stress impairment in cortical-lesioned chronic mild stressed rats.

    abstract::In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a lef...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666141021143333

    authors: Pan J,Liu H,Zhou J,Liu Z,Yang Y,Peng Y,You H,Yang D,Xie P

    更新日期:2014-01-01 00:00:00

  • Molecular mechanisms and pathophysiology of necrotic cell death.

    abstract::Necrotic cell death has long been considered an accidental and uncontrolled mode of cell death. But recently it has become clear that necrosis is a molecularly regulated event that is associated with pathologies such as ischemia-reperfusion (IR) injury, neurodegeneration and pathogen infection. The serine/threonine ki...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408784221306

    authors: Vanlangenakker N,Vanden Berghe T,Krysko DV,Festjens N,Vandenabeele P

    更新日期:2008-05-01 00:00:00

  • Continuing education of the immune system--dendritic cells, immune regulation and tolerance.

    abstract::T cells, as they develop in the thymus come to express antigen receptors. The specificity of these receptors cannot be predicted and must include many with potential anti-self reactivity. Those that encounter self-antigens, in association with self-MHC (major histocompatibility complex), with high affinity are inactiv...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524013363573

    authors: Huang FP,MacPherson GG

    更新日期:2001-09-01 00:00:00

  • Molecular mechanisms of resistance to antiviral therapy in patients with chronic hepatitis B.

    abstract::Similar to the human immunodeficiency virus (HIV), the hepatitis B virus (HBV) replicates via reverse transcription, in this case, within infected hepatocytes. Substantial advances have been achieved in the past ten years in developing and utilizing nucleoside/nucleotide analog drugs to inhibit HBV replication. Most a...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652407780059159

    authors: Yuan HJ,Lee WM

    更新日期:2007-03-01 00:00:00

  • PRAME/EZH2-mediated regulation of TRAIL: a new target for cancer therapy.

    abstract::The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a cancer cell-specific pro-apoptotic activity. This property made the TRAIL associated pathway one of the most promising strategies aimed at inducing tumor-selective death. In fact, several approaches have been considered to explore this pathwa...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652413804810727

    authors: De Carvalho DD,Mello BP,Pereira WO,Amarante-Mendes GP

    更新日期:2013-02-01 00:00:00

  • High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC.

    abstract::Pancreatic Adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide. A variety of mechanisms are involved in PDAC biological behaviors, of which, the mechanisms of immune escape may be a pivotal hallmark. HLA-G is a tolerant molecule implicated in tumor escape and serves as a prognostic biomarker in ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524015666150401102218

    authors: Xu YF,Lu Y,Cheng H,Jiang J,Xu J,Long J,Liu L,Ni Q,Liu C,Yu XJ

    更新日期:2015-01-01 00:00:00

  • Von Hippel-Lindau disease.

    abstract::Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524043359827

    authors: Maher ER

    更新日期:2004-12-01 00:00:00

  • Cytokine Expression Profile in Aqueous Humor and Sera of Patients with Acute Anterior Uveitis.

    abstract:PURPOSE:To evaluate cytokine expression profile in aqueous humor and sera in patients with HLAB27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:Twenty patients with AAU and 17 controls were recruited from August 2012 to March 2013. Study subjects with uveitis were divided into two groups: 9 patie...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524015666150731100012

    authors: Chen W,Zhao B,Jiang R,Zhang R,Wang Y,Wu H,Gordon L,Chen L

    更新日期:2015-01-01 00:00:00

  • Clinical and genetic features of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome.

    abstract::WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL1...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411795677963

    authors: Dotta L,Tassone L,Badolato R

    更新日期:2011-06-01 00:00:00