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Journal of Virology, April 2002, p. 3558-3563, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3558-3563.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Redirecting Retroviral Tropism by Insertion of Short, Nondisruptive Peptide Ligands into Envelope

Timothy J. Gollan and Michael R. Green*

Programs in Gene Function and Expression and in Molecular Medicine, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Received 16 August 2001/ Accepted 20 December 2001

A potentially powerful approach for in vivo gene delivery is to target retrovirus to specific cells through interactions between cell surface receptors and appropriately modified viral envelope proteins. Previously, relatively large (>100 residues) protein ligands to cell surface receptors have been inserted at or near the N terminus of retroviral envelope proteins. Although viral tropism could be altered, the chimeric envelope proteins lacked full activity, and coexpression of wild-type envelope was required for production of transducing virus. Here we analyze more than 40 derivatives of ecotropic Moloney murine leukemia virus (MLV) envelope, containing insertions of short RGD-containing peptides, which are ligands for integrin receptors. In many cases pseudotyped viruses containing only the chimeric envelope protein could transduce human cells. The precise location, size, and flanking sequences of the ligand affected transduction specificity and efficiency. We conclude that retroviral tropism can be rationally reengineered by insertion of short peptide ligands and without the need to coexpress wild-type envelope.

* Corresponding author. Mailing address: Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 364 Plantation St., Worcester, MA 01605. Phone: (508) 856-5331. Fax: (508) 856-5473. E-mail: michael.green{at}umassmed.edu.

Journal of Virology, April 2002, p. 3558-3563, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3558-3563.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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