Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.

A spliced cDNA spanning the Epstein-Barr virus BZLF1 gene expresses the BZLF1 protein and is active in inducing the virus productive cycle. A deletion mutant which lacks the N-terminal half of the protein is inactive. Cotransfection experiments in EBV-negative B-lymphocyte cell lines demonstrated that the BZLF1 gene activates the promoter for the BSLF2 + BMLF1 gene in the absence of any other EBV gene product. These results confirmed that the spliced BZLF1 gene is the transactivating gene structure in BamHI-Z.

Fast skeletal muscles of mdx (X chromosome-linked muscular dystrophy) mice were injected after birth with a recombinant adenovirus containing a minidystrophin gene, a 6.3-kbp cDNA coding for the N-and Cterminal ends ofdystrophin. Adult muscles were challenged by forced lengthening during tetanic contractions. Stretchinduced mechanical and histological damages were much reduced in injected muscles, in (n = 7) or with the Ad-RSVI3gal (n = 7). When mice were 4 months old muscles were isolated under general anesthesia, which preserved circulation. The lateral part of the muscle was dissected out. The order of dissection of the Ad-RSVmDys limb vs. the other one was alternated from animal to animal.Isolated muscles were submitted to repetitive stimulations (125 Hz) for 300 msec, at 5-min intervals. During the first 160 msec, tension was developed isometrically and then a forced lengthening (1 mm; i.e., +7%, at 11.1 mm/sec) was imposed.After relaxation the muscle was returned to the resting length.Histology. At the end of the experiments, the muscles were soaked for 3 h in an oxygenated Krebs

AdmATF is a recombinant adenovirus encoding a secreted within and at the vicinity of the injection site was also supversion of the amino-terminal fragment (ATF) of murine pressed, suggesting that AdmATF inhibited primary tumor urokinase (uPA). This defective adenovirus was used in growth by targeting angiogenesis. AdmATF also interfered three murine models to assess the antitumoral effects with tumor cell establishment at distant sites: (1) lung disassociated with local or systemic delivery of ATF, a broad semination of Lewis lung carcinoma cells was significantly cell invasion inhibitor that antagonizes uPA binding to its reduced following intratumoral injection at the primary site; cell surface receptor (uPAR). A single intratumoral injection and (2) systemic administration of AdmATF inhibited subof AdmATF into pre-established MDA-MB-231 human sequent liver metastasis in a LS174T human colon carcibreast xenografts grown in athymic mice, or into pre-estabnoma xenograft model. These data outline the potential of lished C57/BL6 syngeneic Lewis lung carcinoma resulted using a recombinant adenovirus directing the secretion of an in a specific arrest of tumor growth. Neovascularization antagonist of cell-associated uPA for cancer gene therapy.