GSBS Student Publications
Title
Redirecting retroviral tropism by insertion of short, nondisruptive peptide ligands into envelope
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Programs in Gene Function and Expression and in Molecular Medicine
Date
3-9-2002
Document Type
Article
Medical Subject Headings
3T3 Cells; Amino Acid Sequence; Animals; Genetic Vectors; Humans; Integrins; Ligands; Mice; Molecular Sequence Data; Moloney murine leukemia virus; Oligopeptides; Recombinant Fusion Proteins; Recombination, Genetic; Retroviridae; Transduction, Genetic; Tumor Cells, Cultured; Viral Envelope Proteins
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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.
Rights and Permissions
Citation: J Virol. 2002 Apr;76(7):3558-63.
Related Resources
Journal Title
Journal of virology
PubMed ID
11884580
Repository Citation
Gollan, Timothy J. and Green, Michael R., "Redirecting retroviral tropism by insertion of short, nondisruptive peptide ligands into envelope" (2002). GSBS Student Publications. 400.
https://escholarship.umassmed.edu/gsbs_sp/400