Construction of an adenovirus type 7a E1A- vector

Abstract

A strategy for constructing replication-defective adenovirus vectors from non-subgroup C viruses has been successfully demonstrated with adenovirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a reporter virus expressing the chloramphenicol acetyltransferase (CAT) gene from the cytomegalovirus promoter enhancer was constructed with DNA fragments isolated from Ad7a, an Ad7a recombination reporter plasmid, and the 293 cell line. The Ad7a-CAT virus particle transduces A549 cells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tissues, with maximal levels of CAT gene expression found in the liver. The duration of Ad7a-CAT transgene expression in the liver was maximally maintained 2 weeks postinfection, with a decline to baseline activity by the week 4 postinfection. Ad7a-CAT represents the first example of a non-subgroup C E1A ؊ adenovirus gene transfer vector.

The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3

“…Interestingly, these vectors show an extended tropism compared to species C vectors and infect hematopoietic and dendritic cells. Similarly, replica-tion-competent or replication-defective viral vectors derived from Ad7 have been used for vaccine strategies (Abrahamsen et al, 1997;Lubeck et al, 1989;Nan et al, 2003). An extended tropism was also demonstrated for fiber swapped Ad vectors containing fibers of species B viruses such as Ad3 (Kanerva et al, 2002;Stevenson et al, 1997;Von Seggern et al, 2000), Ad11 (Stecher et al, 2001), and Ad35 Havenga et al, 2002;Knaan-Shanzer et al, 2001;Rea et al, 2001;Shayakhmetov et al, 2000;Yotnda et al, 2001).…”

Adenovirus receptors: implications for tropism, treatment and targeting

“…Despite this, Ads are the most frequently used vectors for human gene therapy and cancer therapy [4]. The strategies employed to solve these problems have therefore shifted to (1) using human non-species C [5][6][7][8][9][10], human chimeric [11][12][13][14] or non-human [15][16][17][18] Ad vectors in order to avoid the immune response, and (2) detargeting vectors away from the liver and retargeting them to cells and tissues of interest. To achieve these goals, efforts have also been made to identify the molecules and mechanisms that mediate Ad binding to target cells (Figures 1 and 2; Table 1)-subjects that are discussed in this review.…”

State‐of‐the‐art human adenovirus vectorology for therapeutic approaches

“…To further expand the diversity of Ad vectors, nonspecies C viruses were vectorized, which were initially mainly based on species B Ads. The first species B Ad which was converted into a replication‐deficient vector was HAdV‐B7 . In 2003, several groups showed the development of HAdV‐B35 vectors , and in 2004 and 2005, HAdV‐B3 and HAdV‐B11 vectors were published .…”