Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector

被引:139
作者
Reynolds, PN [1 ]
Dimitriev, I [1 ]
Curiel, DT [1 ]
机构
[1] Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35294 USA
关键词
adenovirus; gene therapy; targeting; in vivo;
D O I
10.1038/sj.gt.3300941
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adenoviral vectors are attractive gene delivery vehicles, but their in vivo utility is reduced by lack of cell-specific infection. Tropism modification of the virion by genetic manipulation of capsid proteins is an attractive strategy to achieve targeted transduction. However, no genetic targeting strategies have yet been shown to modify the distribution of transgene expression following systemic administration of vector. This is an essential requirement if such approaches are to form a basis for further vector development. In this report we present data showing that insertion of a RGD motif into the HI loop of the adenoviral fiber knob results in a significant change in transgene expression profile following intravenous administration. The key finding that a motif in the HI loop is available for cellular interaction when administered systemically means that such modifications can be rationally considered as a foundation upon which further genetic modifications can be superimposed for targeted systemic gene therapy.
引用
收藏
页码:1336 / 1339
页数:4
相关论文
共 23 条
  • [1] Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5
    Bergelson, JM
    Cunningham, JA
    Droguett, G
    KurtJones, EA
    Krithivas, A
    Hong, JS
    Horwitz, MS
    Crowell, RL
    Finberg, RW
    [J]. SCIENCE, 1997, 275 (5304) : 1320 - 1323
  • [2] ADENOVIRUS-MEDIATED IN-VIVO GENE-TRANSFER
    BRODY, SL
    CRYSTAL, RG
    [J]. GENE THERAPY FOR NEOPLASTIC DISEASES, 1994, 716 : 90 - 103
  • [3] An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism
    Dmitriev, I
    Krasnykh, V
    Miller, CR
    Wang, MH
    Kashentseva, E
    Mikheeva, G
    Belousova, N
    Curiel, DT
    [J]. JOURNAL OF VIROLOGY, 1998, 72 (12) : 9706 - 9713
  • [4] Targeted gene delivery by tropism-modified adenoviral vectors
    Douglas, JT
    Rogers, BE
    Rosenfeld, ME
    Michael, SI
    Feng, MZ
    Curiel, DT
    [J]. NATURE BIOTECHNOLOGY, 1996, 14 (11) : 1574 - 1578
  • [5] Goldman CK, 1997, CANCER RES, V57, P1447
  • [6] Adenovirus type 5 fiber knob binds to MHC class I alpha 2 domain at the surface of human epithelial and B lymphoblastoid cells
    Hong, SS
    Karayan, L
    Tournier, J
    Curiel, DT
    Boulanger, PA
    [J]. EMBO JOURNAL, 1997, 16 (09) : 2294 - 2306
  • [7] KASONO K, IN PRESS CLIN CANC R
  • [8] Characterization of an adenovirus vector containing heterologous peptide epitope in the HI loop of the fiber knob
    Krasnykh, V
    Dmitriev, I
    Mikheeva, G
    Miller, CR
    Belousova, N
    Curiel, DT
    [J]. JOURNAL OF VIROLOGY, 1998, 72 (03) : 1844 - 1852
  • [9] Miller CR, 1998, CANCER RES, V58, P5738
  • [10] alpha v Integrins as receptors for tumor targeting by circulating ligands
    Pasqualini, R
    Koivunen, E
    Ruoslahti, E
    [J]. NATURE BIOTECHNOLOGY, 1997, 15 (06) : 542 - 546