Adeno-associated virus types 5 and 6 use distinct receptors for cell entry

Michael P SEILER; A. Dusty MILLER; Joseph ZABNER; Christine L HALBERT

doi:10.1089/hum.2006.17.10

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Adeno-associated virus types 5 and 6 use distinct receptors for cell entry

Journal article

Peer reviewed

Adeno-associated virus types 5 and 6 use distinct receptors for cell entry

Michael P SEILER, A. Dusty MILLER, Joseph ZABNER and Christine L HALBERT

Human gene therapy, Vol.17(1), pp.10-19

2006

DOI: 10.1089/hum.2006.17.10

PMID: 16409121

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Abstract

The transduction efficiency of adeno-associated virus (AAV) vectors in various somatic tissues is determined primarily by the viral capsid proteins. In contrast to vectors made with AAV type 2 capsids, those having type 5 or 6 capsids show high transduction rates in airway epithelial cells, in a range that should be sufficient for treating lung disease. Here we have compared the properties of vectors made with AAV5 or AAV6 capsid proteins to determine whether their receptor usage is similar, and found several differences between the viruses. First, an AAV6 vector did not hemagglutinate red blood cells, whereas an AAV5 vector did, and this property was sialic acid dependent. Second, AAV5 vector transduction required sialic acid in all cells tested, whereas AAV6 vector transduction was sialic acid dependent or independent, depending on the target cells tested. Third, levels of an AAV6 vector that interfered with entry of another AAV6 vector only poorly inhibited AAV5 vector transduction and vice versa. These results indicate that AAV5 and AAV6 vectors use distinct cellular receptors for cell entry. Although both AAV5 and AAV6 vectors exhibited high transduction rates in well-differentiated human airway epithelial cultures, they exhibited distinct cell-type transduction profiles in mouse lung that may reflect differences in receptor usage.

Biotechnology

Gene Therapy

Miscellaneous

Transfusions. Complications. Transfusion reactions. Cell and gene therapy

Biological and medical sciences

Molecular and cellular biology

Medical sciences

Cell structures and functions

Fundamental and applied biological sciences. Psychology

Cell receptors

Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy

Health. Pharmaceutical industry

Industrial applications and implications. Economical aspects

Applied cell therapy and gene therapy

Details

Title: Subtitle: Adeno-associated virus types 5 and 6 use distinct receptors for cell entry
Creators: Michael P SEILER - Deparment of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States
A. Dusty MILLER - Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Joseph ZABNER - Deparment of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States
Christine L HALBERT - Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Resource Type: Journal article
Publication Details: Human gene therapy, Vol.17(1), pp.10-19
Publisher: Liebert
DOI: 10.1089/hum.2006.17.10
PMID: 16409121
ISSN: 1043-0342
eISSN: 1557-7422
Language: English
Date published: 2006
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094219702771

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