公开(公告)号：WO1998032860A1

公开(公告)日：1998-07-30

申请号：PCT/US1997023685

申请日：1997-12-19

Applicant: BAXTER INTERNATIONAL INC.

Inventor： BAXTER INTERNATIONAL INC. ,  DAI, Yifan

IPC: C12N15/33

CPC classification number: C12N15/86 ,  C12N2710/10343

Abstract: The invention provides reagents and methods for highly efficient generation of adenoviral vectors by homologous recombination. The present invention provides unique shuttle vectors and an improved methodology for co-transfection of a shuttle vector and a helper plasmid into 293 cells to generate E1-deleted, E1 / E3-deleted, E1 / E2a / E3-deleted or E1 / E3 / E4 / protein IX-deleted adenoviral vectors.

Abstract translation: 本发明提供了通过同源重组高效产生腺病毒载体的试剂和方法。 本发明提供独特的穿梭载体和用于将穿梭载体和辅助质粒共转染293细胞以产生E1缺失的E1 / E3缺失的E1 / E2a / E3缺失或E1 / E3 / E4 /蛋白IX缺失的腺病毒载体。

公开(公告)号：EP0954591A2

公开(公告)日：1999-11-10

申请号：EP97928961.0

申请日：1997-05-30

Applicant: BAXTER INTERNATIONAL INC.

Inventor： ZHANG, Wei-Wei ,  ALEMANY, Ramon ,  DAI, Yifan ,  JOSEPHS, Steven ,  BALAGUE, Cristina ,  AYARES, David ,  SCHNEIDERMAN, Richard

IPC: A01K67 ,  A61K31 ,  A61K35 ,  A61K38 ,  A61K48 ,  A61P7 ,  C07K14 ,  C12N5 ,  C12N7 ,  C12N15 ,  C12Q1 ,  G01N21 ,  G01N33

CPC classification number: C12N15/8509 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2217/20 ,  A01K2267/0306 ,  A61K38/00 ,  A61K48/00 ,  C07K14/755 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2800/108 ,  C12N2800/30 ,  C12N2810/859 ,  C12N2830/003 ,  C12N2830/008 ,  C12N2830/38 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/206

Abstract: This invention is related to adenoviral (Ad) vectors and their applications in the field of genetic medicine, including gene transfer, gene therapy, and gene vaccination. More specifically, this invention is related to the Ad vectors that carry the minimal cis-element of the Ad genome (mini-Ad vector) and are capable of delivering transgenes and/or heterologous DNA up to 36 kb. The generation and propagation of the mini-Ad vectors require trans-complementation of a packaging-attenuated and replication-defective helper Ad (helper) in an Ad helper cell line. This invention further comprises a methodology for generating a mini-adenoviral (mini-Ad) vector for use in gene therapy of hemophilia and animal test systems for in vivo evaluation of the Ad vectors. More specifically, this invention describes factor VIII (FVIII) Ad vectors that only contain minimal cis-element of the Ad genome (so-called mini-Ad) and comprise a human FVIII cDNA with other supporting DNA elements up to 36 kb. The FVIII mini-Ad can be generated and preferentially amplified through the assistance of a packaging-attenuated helper Ad and a helper cell line. This invention also reports designs and methods for producing transgenic mouse models that can be used for in vivo testing the mini-Ad.