Compositions and methods for modulating vascular development

Inactive Publication Date: 2007-02-08
GENENTECH INC
View PDF1 Cites 21 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011] The present invention is based on the identification and characterization of a novel EC-derived secreted factor, EGF-like domain 7 (EGFL7). EGFL7 is expressed at high levels in the vasculature associated with tissue proliferation, and is down-regulated in most of the mature vessels in normal adult tissues. Loss of EGFL7 function caused significant vascular defects in animal embryos, and reduced tumor growth. Based on its structure, expression and activity, EGFL

Problems solved by technology

Loss of EGFL7 function caused significant vascular

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compositions and methods for modulating vascular development
  • Compositions and methods for modulating vascular development
  • Compositions and methods for modulating vascular development

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cloning of EGFL7

[0318] EGFL7 was identified and cloned in an effort to discover novel human secreted and transmembrane proteins, particularly those involved in the regulation of vascular development. Details of the cloning and expression of human EGFL7 are described in, for example, patent application US20030224948A1 (wherein EGFL7 is identified as PRO1449). Briefly, whole mount in situ hybridization screens were performed to identify secreted factors and receptors that are enriched in mouse embryonic vasculatures. By way of signal sequence prediction and extracellular domain homology searching, hundreds of human and mouse cDNAs representing putative secreted factors and receptors were identified and collected. Using the mouse cDNAs as templates, riboprobes were generated and in situ hybridizations were performed on whole mouse embryos ranging from E7.5 to E14.5. This developmental time window was chosen because it encompasses many key stages in vasculogenesis and angiogenesis. Amo...

example 2

Expression of EGFL7

[0326] To elucidate the expression pattern of EGFL7, whole mount in situ hybridization, immunofluorescent staining and radioactive in situ hybridization were carried out on mouse and zebrafish embryos as well as mouse and human tissue sections.

[0327] Zebrafish and Mouse Strains

[0328] Mouse embryos were harvested from timed-pregnant CD-1 mice. Tüebingen long fin (TL) wild-type zebrafish line, ˜30 hpf cloche (Clom39) homozygous mutant embryos and their wild-type siblings were used in the expression and activity studies described herein below. Adult zebrafish and embryos were maintained as previously described (Westerfield 1993 Zebrafish Book).

[0329] Radioactive in situ Hybridization

[0330] Tissues were processed for in situ hybridization by a method described previously. Phillips et al. (1990) Science 250:290-4. 33P-UTP-labelled RNA probes were generated as described. Melton et al. (1984) Nucleic Acids Research 12:7035-56. EGFL7 sense and antisense probes were s...

example 3

Phenotypic Analysis of Animals with Reduced EGFL7 Activity

[0343] A. Vascular Defects in the EGFL7 Knockdown Zebrafish

[0344] In a recent report, conditioned medium containing the recombinant EGFL7 protein is shown to inhibit smooth muscle cell (SMC) migration in vitro. Soncin et al. EMBO J. 22:5700-5711 (2003). However, its in vivo function has not been defined. To uncover the in vivo biological function of EGFL7, the model organism zebrafish was used because of the availability of tools to study vasculogenesis and angiogenesis, and the ease to manipulate gene expression in embryos. Fishman et al. Circulation Research 74:757-63 (1994); Weinstein et al. Cardiovascular Research 31 :E17-24 (1996); Dooley et al. Current Opinion in Genetics &Development 10:252-6(2000); Nasevicius & Ekker Nature Genetics 26:216-20 (2000). Furthermore, it was found that Egfl8 was expressed in a subset of blood vessels and peripheral nerves in mouse embryos, making it a potential redundant factor for EGFL7...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Chemotherapeutic propertiesaaaaaaaaaa
Cell growthaaaaaaaaaa
Login to view more

Abstract

The present invention provides methods of using EGFL7 antagonist to modulate vascular development. Also provided herein are methods of screening for modulators of EGFL7 activity. Furthermore, methods of treatment using EGFL7 antagonists are provided.

Description

RELATED APPLICATIONS [0001] This application is a continuation of International Application No. PCT / US2005 / 013658, filed Apr. 14, 2005, which claims the benefit of U.S. Provisional Application No. 60 / 562,054, filed Apr. 14, 2004.FIELD OF THE INVENTION [0002] The present invention relates generally to compositions and methods that are useful for modulating vascular development. Specifically, the present invention relates to EGF-like domain 7 (EGFL7), a novel endothelial cell-derived secreted factor. The present invention further relates to the diagnosis and treatment of conditions and diseases associated with angiogenesis. BACKGROUND OF THE INVENTION [0003] Development of a vascular supply is a fundamental requirement for many physiological and pathological processes. Actively growing tissues such as embryos and tumors require adequate blood supply. They satisfy this need by producing pro-angiogenic factors, which promote new blood vessel formation via a process called angiogenesis. ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K39/395A61K31/7088C07K16/22
CPCA61K31/7088C07K16/22A61K2039/505A61P17/00A61P17/06A61P27/00A61P27/02A61P27/06A61P29/00A61P35/00A61P35/04A61P37/06A61P43/00A61P9/00A61P9/10A61K39/395
Inventor FILVAROFF, ELLENYE, WEILANPARKER, LEON H. IVHONGO, JO-ANNE S.SCHMIDT, MAIKE
Owner GENENTECH INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap