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Methods for Increasing the Selective Efficacy of Gene Therapy Using CAR Peptide and Heparan Sulfate Mediated Macropinocytosis

a car peptide and macropinocytosis technology, applied in the field of molecular medicine, can solve the problems of little known about their roles in vitro and in vivo, and achieve the effects of improving enhancing macropinocytosis, and increasing the selective efficacy of gene therapy

Inactive Publication Date: 2017-10-26
VASCULAR BIOSCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, little is known about their roles both in vitro and in vivo.

Method used

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  • Methods for Increasing the Selective Efficacy of Gene Therapy Using CAR Peptide and Heparan Sulfate Mediated Macropinocytosis
  • Methods for Increasing the Selective Efficacy of Gene Therapy Using CAR Peptide and Heparan Sulfate Mediated Macropinocytosis
  • Methods for Increasing the Selective Efficacy of Gene Therapy Using CAR Peptide and Heparan Sulfate Mediated Macropinocytosis

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examples

[0083]Recent experiments (Urakami et al. 2011; Toba et al. (in submission)) have demonstrated the ability of the pulmonary hypertensive homing, cell-penetrating peptide CARSKNKDC (CAR) (FIG. 2) to enhance the effects of co-administered vasodilators (fasudil, Y-27632, imatimib, and sildenafil) in selectively lowering pulmonary pressure in animal models of pulmonary arterial hypertension (PAH). Here we provide a hypothesis for CAR's mechanism of action and identify a putative receptor.

Methods

[0084]We examined data on enzymatic specificity from the literature and combined it with genetic expression in a porcine model of pulmonary hypertension to arrive at a likely target for CAR. In previous experiments, cell-surface heparan sulfate (HS) was shown to be necessary for both CAR binding and internalization (Jarvinen et al. 2007). When treated with heparinase I and III, binding of CAR to Chinese hamster ovary cells was greatly reduced. This suggested that CAR's specific binding and interna...

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Abstract

Disclosed are compositions and methods for triggering disease selective macropinocytosis. The compositions can serve as a marker of disease activity and as a trigger of enhanced macropinocytosis in tissues undergoing disease remodeling such as wound healing, cancer, PAH, inflammation, diabetes, Crohn's disease, ulcerative colitis, ankylosing spondylitis, diseases of the endometrium, psoriasis, irritable bowel syndrome, arthritis, fibrotic disorders, interstitial cystitis, autoimmune diseases, asthma, acute lung injury, and adult respiratory distress syndrome. The compositions can also serve as a receptor for disease selective cell penetrating peptides in the cells and extracellular matrix of diseased tissues.

Description

RELATED APPLICATIONS[0001]This application is a divisional application claiming priority from United States National Stage application Ser. No. 14 / 649,455, filed Jun. 3, 2015, now U.S. Pat. No. 9,603,890, claiming priority under 35 U.S.C. 371 from International Patent Application No. PCT / US13 / 72768 filed on Dec. 3, 2013, which claims priority from U.S. Provisional Application No. 61 / 732,859, filed on Dec. 3, 2012, the contents of which are hereby incorporated by reference herein.FIELD OF THE INVENTION[0002]The present invention relates generally to the field of molecular medicine, and specifically to cell and tissue targeting peptides.BACKGROUND OF THE INVENTION[0003]Cell penetrating peptides were first discovered through efforts to describe how HIV (Human Immunodefficiency Virus) enters cells (Frankel 1988, Green 1988). This led to the discovery of the TAT (Trans-Activator of Transcription) protein encoded as the TAT gene within the HIV-1 virus as the protein responsible for cell p...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/08G01N33/68A61K45/06C12Q1/34
CPCC12Q1/34G01N2800/12A61K45/06G01N2333/926G01N2800/321G01N33/6893A61K38/08
Inventor MANN, DAVID
Owner VASCULAR BIOSCI
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