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Title: Structure of adenovirus bound to cellular receptor car

Abstract

Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.

Inventors:
Issue Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1174848
Patent Number(s):
6737234
Application Number:
09/389,603
Assignee:
Brookhaven Science Associates, LCC (Upton, NY)
Patent Classifications (CPCs):
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
DOE Contract Number:  
AC02-98CH10886
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Freimuth, Paul I. Structure of adenovirus bound to cellular receptor car. United States: N. p., 2004. Web.
Freimuth, Paul I. Structure of adenovirus bound to cellular receptor car. United States.
Freimuth, Paul I. Tue . "Structure of adenovirus bound to cellular receptor car". United States. https://www.osti.gov/servlets/purl/1174848.
@article{osti_1174848,
title = {Structure of adenovirus bound to cellular receptor car},
author = {Freimuth, Paul I.},
abstractNote = {Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2004},
month = {5}
}

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Works referenced in this record:

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journal, May 1997


Gene therapy using adenoviral vectors
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Human adenovirus type 41 contains two fibers
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Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
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A Single Amino Acid in the Adenovirus Type 37 Fiber Confers Binding to Human Conjunctival Cells
journal, April 1999


Adenovirus-mediated gene transfer into striated muscles
journal, April 1995


Crystal structure of the receptor-binding domain of adenovirus type 5 fiberprotein at 1.7 Å resolution
journal, December 1994