PortalPublikationenIncorporation of tumor-targeting peptides into recombinant a...

Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids

Standard

Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. / Grifman, M; Trepel, M; Speece, P; Gilbert, L B; Arap, Wadih; Pasqualini, Renata; Weitzman, Matthew D.

in: MOL THER, Jahrgang 3, Nr. 6, 06.2001, S. 964-75.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Grifman, M, Trepel, M, Speece, P, Gilbert, LB, Arap, W, Pasqualini, R & Weitzman, MD 2001, 'Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids', MOL THER, Jg. 3, Nr. 6, S. 964-75. https://doi.org/10.1006/mthe.2001.0345

APA

Grifman, M., Trepel, M., Speece, P., Gilbert, L. B., Arap, W., Pasqualini, R., & Weitzman, M. D. (2001). Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. MOL THER, 3(6), 964-75. https://doi.org/10.1006/mthe.2001.0345

Vancouver

Grifman M, Trepel M, Speece P, Gilbert LB, Arap W, Pasqualini R et al. Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. MOL THER. 2001 Jun;3(6):964-75. https://doi.org/10.1006/mthe.2001.0345

Bibtex

@article{4f9fe40acca742649ba4de132fbf0f1e,
title = "Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids",
abstract = "The human parvovirus adeno-associated virus type 2 (AAV-2) possesses many features that make it an attractive vector for gene delivery in vivo. However, its broad host range may limit its usefulness and effectivity in several gene therapy applications in which transgene expression needs to be limited to a specific organ or cell type. In this study, we explored the possibility of directing recombinant AAV-2 transduction by incorporating targeting peptides previously isolated by in vivo phage display. Two putative loops within the AAV-2 capsid were examined as sites for incorporation of peptides. We tested the effects of deleting these loops and different strategies for the incorporation of several targeting peptides. The tumor-targeting sequence NGRAHA and a Myc epitope control were incorporated either as insertions or as replacements of the original capsid sequence. Viruses were assessed for packaging, accessibility of incorporated peptides, heparin binding, and transduction in a range of cell lines. Whereas recombinant viruses containing mutant capsid proteins were produced efficiently, transduction of several cell lines was significantly impaired for most modifications. However, certain mutants containing the peptide motif NGR, which binds CD13 (a receptor expressed in angiogenic vasculature and in many tumor cell lines), displayed an altered tropism toward cells expressing this receptor. Based on this work and previous studies, possible strategies for achieving in vivo targeting of recombinant AAV-2 are discussed.",
keywords = "Amino Acid Sequence, Antigens, CD13, Blotting, Western, Capsid, DNA, DNA Primers, Dependovirus, Genes, myc, Green Fluorescent Proteins, Heparin, Humans, Luminescent Proteins, Molecular Sequence Data, Mutation, Oligopeptides, Parvovirus, Polymerase Chain Reaction, Receptors, Virus, Sequence Homology, Amino Acid, Transduction, Genetic, Tumor Cells, Cultured, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.",
author = "M Grifman and M Trepel and P Speece and Gilbert, {L B} and Wadih Arap and Renata Pasqualini and Weitzman, {Matthew D}",
year = "2001",
month = jun,
doi = "10.1006/mthe.2001.0345",
language = "English",
volume = "3",
pages = "964--75",
journal = "MOL THER",
issn = "1525-0016",
publisher = "NATURE PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids

AU - Grifman, M

AU - Trepel, M

AU - Speece, P

AU - Gilbert, L B

AU - Arap, Wadih

AU - Pasqualini, Renata

AU - Weitzman, Matthew D

PY - 2001/6

Y1 - 2001/6

N2 - The human parvovirus adeno-associated virus type 2 (AAV-2) possesses many features that make it an attractive vector for gene delivery in vivo. However, its broad host range may limit its usefulness and effectivity in several gene therapy applications in which transgene expression needs to be limited to a specific organ or cell type. In this study, we explored the possibility of directing recombinant AAV-2 transduction by incorporating targeting peptides previously isolated by in vivo phage display. Two putative loops within the AAV-2 capsid were examined as sites for incorporation of peptides. We tested the effects of deleting these loops and different strategies for the incorporation of several targeting peptides. The tumor-targeting sequence NGRAHA and a Myc epitope control were incorporated either as insertions or as replacements of the original capsid sequence. Viruses were assessed for packaging, accessibility of incorporated peptides, heparin binding, and transduction in a range of cell lines. Whereas recombinant viruses containing mutant capsid proteins were produced efficiently, transduction of several cell lines was significantly impaired for most modifications. However, certain mutants containing the peptide motif NGR, which binds CD13 (a receptor expressed in angiogenic vasculature and in many tumor cell lines), displayed an altered tropism toward cells expressing this receptor. Based on this work and previous studies, possible strategies for achieving in vivo targeting of recombinant AAV-2 are discussed.

AB - The human parvovirus adeno-associated virus type 2 (AAV-2) possesses many features that make it an attractive vector for gene delivery in vivo. However, its broad host range may limit its usefulness and effectivity in several gene therapy applications in which transgene expression needs to be limited to a specific organ or cell type. In this study, we explored the possibility of directing recombinant AAV-2 transduction by incorporating targeting peptides previously isolated by in vivo phage display. Two putative loops within the AAV-2 capsid were examined as sites for incorporation of peptides. We tested the effects of deleting these loops and different strategies for the incorporation of several targeting peptides. The tumor-targeting sequence NGRAHA and a Myc epitope control were incorporated either as insertions or as replacements of the original capsid sequence. Viruses were assessed for packaging, accessibility of incorporated peptides, heparin binding, and transduction in a range of cell lines. Whereas recombinant viruses containing mutant capsid proteins were produced efficiently, transduction of several cell lines was significantly impaired for most modifications. However, certain mutants containing the peptide motif NGR, which binds CD13 (a receptor expressed in angiogenic vasculature and in many tumor cell lines), displayed an altered tropism toward cells expressing this receptor. Based on this work and previous studies, possible strategies for achieving in vivo targeting of recombinant AAV-2 are discussed.

KW - Amino Acid Sequence

KW - Antigens, CD13

KW - Blotting, Western

KW - Capsid

KW - DNA

KW - DNA Primers

KW - Dependovirus

KW - Genes, myc

KW - Green Fluorescent Proteins

KW - Heparin

KW - Humans

KW - Luminescent Proteins

KW - Molecular Sequence Data

KW - Mutation

KW - Oligopeptides

KW - Parvovirus

KW - Polymerase Chain Reaction

KW - Receptors, Virus

KW - Sequence Homology, Amino Acid

KW - Transduction, Genetic

KW - Tumor Cells, Cultured

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1006/mthe.2001.0345

DO - 10.1006/mthe.2001.0345

M3 - SCORING: Journal article

C2 - 11407911

VL - 3

SP - 964

EP - 975

JO - MOL THER

JF - MOL THER

SN - 1525-0016

IS - 6

ER -