Improved gene delivery to B lymphocytes using a modified adenovirus vector targeting CD21

被引:10
作者
Mailly, Laurent [1 ]
Renaut, Laurence [1 ]
Rogee, Sophie [1 ]
Grellier, Elodie [1 ]
D'Halluin, Jean-Claude [1 ]
Colin, Morvane [1 ]
机构
[1] Univ Lille 2, Inst Rech Canc Lille, INSERM, U817, F-59045 Lille, France
关键词
adenovirus; B lymphocytes; fiber; retargeting; gene transfer; intracellular trafficking; endosomolysis; CD21; HEMATOPOIETIC-CELL LINES; FIBER KNOB; RECEPTOR; THERAPY; TROPISM; BINDING; TRANSDUCTION; EFFICIENCY; PROTEIN; IDENTIFICATION;
D O I
10.1016/j.ymthe.2006.03.017
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Gene transfer by adenoviruses, which are widely used for gene therapy, may provide an alternative approach to treatment of several hematopoietic malignancies. However, a major limitation of adenovirus 5-based gene therapy lies in the natural tropism of the virus for the widely expressed hCAR receptor. The efficacy of adenoviral vectors could be improved if viral vectors that exhibit tissue-specific gene delivery were developed. For efficient gene transfer it is essential that every step from binding of virus to target cells to transgene expression is successfully accomplished. We developed a specific vector targeting the CD21 receptor, by inserting a CD21 binding sequence, derived from the EBV GP350/220 protein, into the HI loop of the HAdV5 fiber protein. This vector, HAdV5-CD21HIloop, binds specifically to CD21-positive cells and results in enhanced expression of the transgene in these cells and reduced expression in CD21-negative cells. Viral infection is highly correlated with the presence of CD21 receptors. Taken together, these results demonstrate that HAdVS-CD21Hlloop is able to transduce CD21-positive cells specifically with reduced infection of nontarget cells. This is the result of the maintenance of the intracellular trafficking of the genetically modified adenovirus without vesicular retention, leading to enhanced nuclear transfer.
引用
收藏
页码:293 / 304
页数:12
相关论文
共 46 条
[1]   Targeted adenoviral vectors [J].
Barnett, BG ;
Crews, CJ ;
Douglas, JT .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2002, 1575 (1-3) :1-14
[2]   Modulation of adenovirus vector tropism via incorporation of polypeptide ligands into the fiber protein [J].
Belousova, N ;
Krendelchtchikova, V ;
Curiel, DT ;
Krasnykh, V .
JOURNAL OF VIROLOGY, 2002, 76 (17) :8621-8631
[3]  
CAREL JC, 1989, J IMMUNOL, V143, P923
[4]   Efficient species CHAdV infectivity in plasmocytic cell lines using a clathrin-inclependent lipid raft/caveola endocytic route [J].
Colin, M ;
Mailly, L ;
Rogée, S ;
D'Halluin, JC .
MOLECULAR THERAPY, 2005, 11 (02) :224-236
[5]   Factors involved in the sensitivity of different hematopoietic cell lines to infection by subgroup C adenovirus: implication for gene therapy of human lymphocytic malignancies [J].
Colin, M ;
Renaut, L ;
Mailly, L ;
D'Halluin, JC .
VIROLOGY, 2004, 320 (01) :23-39
[6]  
COLIN M, 2003, HEMATOLOGY, V9, P303
[7]   ADENOVIRUS TYPE-2 ASSEMBLY ANALYZED BY REVERSIBLE CROSSLINKING OF LABILE INTERMEDIATES [J].
DHALLUIN, JC ;
MARTIN, GR ;
TORPIER, G ;
BOULANGER, PA .
JOURNAL OF VIROLOGY, 1978, 26 (02) :357-363
[8]   Replication-defective vector based on a chimpanzee adenovirus [J].
Farina, SF ;
Gao, GP ;
Xiang, ZQ ;
Rux, JJ ;
Burnett, RM ;
Alvira, MR ;
Marsh, J ;
Ertl, HCJ ;
Wilson, JM .
JOURNAL OF VIROLOGY, 2001, 75 (23) :11603-11613
[9]   High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 up-regulation [J].
Hara, T ;
Suzuki, Y ;
Semba, T ;
Hatanaka, M ;
Matsumoto, M ;
Seya, T .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1995, 42 (06) :581-590
[10]   CD19-targeting liposomes containing imatinib efficiently kill Philadelphia chromosome-positive acute lymphoblastic leukemia cells [J].
Harata, M ;
Soda, Y ;
Tani, K ;
Ooi, J ;
Takizawa, T ;
Chen, MH ;
Bai, YS ;
Izawa, K ;
Kobayashi, S ;
Tomonari, A ;
Nagamura, F ;
Takahashi, S ;
Uchimaru, K ;
Iseki, T ;
Tsuji, T ;
Takahashi, TA ;
Sugita, K ;
Nakazawa, S ;
Tojo, A ;
Maruyama, K ;
Asano, S .
BLOOD, 2004, 104 (05) :1442-1449