摘要:
The invention relates to a replication-deficient adenoviral vector comprising two or more nucleic acid sequences encoding Dengue virus antigens and a chimeric hexon protein. The chimeric hexon protein comprises a first portion and a second portion. The first portion comprises at least 10 contiguous amino acid residues from a first adenovirus serotype (e.g., serotype 5 adenovirus hexon protein), optionally with one amino acid substitution. The second portion comprises (a) at least one hypervariable region (HVR) of a hexon protein of an adenovirus of a second adenovirus serotype, or (b) at least one synthetic hypervariable region (HVR) that is not present in the hexon protein of the wild-type adenovirus of the first adenovirus serotype.
摘要:
The invention provides a method of inducing an immune response against a human immunodeficiency virus (HIV) in a mammal. The method comprises administering to the mammal an adenoviral vector composition comprising one or more adenoviral vectors encoding two or more different HIV antigens, the production of which induces an immune response against HIV in the mammal. The invention also provides an adenoviral vector composition comprising four adenoviral vectors encoding an HIV clade A Env protein, an HIV clade B Env protein, an HIV clade C Env protein, and a fusion protein comprising an HIV clade B Gag protein and Pol protein, respectively.
摘要:
The invention provides methods for propagating a monkey adenovirus in a cell including a human cell, comprising one or more gene products isolated from a human adenovirus. Also provided are methods for propagating wherein the monkey adenovirus comprises a nucleic acid sequence encoding a human adenovirus gene product. The invention further provides a monkey adenovirus. including a replication-deficient monkey adenovirus, obtained by such propagation methods.
摘要:
A recombinant adenovirus comprising a chimeric penton base protein, wherein an RGD amino acid sequence is deleted from the penton base protein, a method of gene therapy involving the use of such adenovirus, and adenoviral transfer vectors for the generation of such recombinant adenovirus are provided.
摘要:
Provided are methods of modulating the persistence of the expression in a cell of a transgene, such as a transgene in a non-Herpes vector or in at least E4Δ adenoviral vector, and related systems. One method comprises contacting the cell with a non-Herpes vector comprising and expressing a gene encoding HSV ICP0, whereupon expression of HSV ICP0 the persistence of expression of the transgene is modulated. Further provided is a system for modulating the persistence of expression of a transgene, which system comprises a non-Herpes vector comprising (i) a gene encoding HSV ICP0 and (ii) a transgene, wherein the HSV ICP0 modulates the persistence of expression of the transgene and either the non-Herpes vector comprises the transgene or the system further comprises a vector, in which case the vector comprises the transgene. Another method comprises contacting the cell with an at least E4Δ adenoviral vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, wherein the trans-acting factor modulates the persistence of expression of the transgene and the gene encoding the trans-acting factor is not from the E4 region of an adenovirus. Yet another method comprises contacting a cell simultaneously or sequentially with (i) an at least E4Δ adenoviral vector comprising a transgene and (ii) a viral vector comprising a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. Also provided is a system for modulating the persistence of expression of a transgene in an at least E4Δ adenoviral vector, which system comprises (i) an at least E4Δ adenoviral vector comprising a transgene and (ii) a gene encoding a trans-acting factor, wherein the gene encoding the trans-acting factor is not from the E4 region of an adenovirus, the trans-acting factor modulates the persistence of expression of the transgene, and either the at least E4Δ adenoviral vector comprises the gene encoding the trans-acting factor or the system comprises a viral vector, in which case the viral vector comprises the gene encoding the trans-acting factor.
摘要:
The present invention provides multiply replication deficient adenoviral vectors having a spacer in at least one replication deficient adenoviral region, as well as complementing cell lines therefor. Also provided are means of constructing the multiply replication deficient adenoviral vectors and methods of use thereof, e.g., in gene therapy.
摘要:
The present invention provides a method for reducing the size of a tumor in a human comprising (a) directly injecting into the tumor, via multiple injections to different points of the tumor, a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) a replication-deficient adenoviral vector comprising a nucleic acid sequence encoding TNF-alpha operably linked to a promoter, wherein the dose comprises about 1x107 to about 4x1012 3 particle units (pu) of replication-deficient adenoviral vector, two or more times over a therapeutic period comprising up to 10 weeks, and (b) administering a dose of ionizing radiation over the duration of the therapeutic period, whereby the size of the tumor is reduced.
摘要:
An adenoviral vector comprising an adenoviral genome comprising (i) at least one deletion in a region of the adenoviral genome selected from the group consisting of E1, E2A and E4, (ii) (a) at least one deletion in the VAI gene of the adenoviral genome, alone or in further combination with at least one deletion in the VAII gene of the adenoviral genome, (b) a recombinant VAI gene, alone or in further combination with a recombinant VAII gene, wherein the recombinant gene comprises either of a regulatable promoter in place of the native promoter or a mutated native promoter and 5' to the mutated native promoter, a pol II promoter, or (c) a dominant negative, double-stranded, RNA-dependent protein kinase (PKR) and, optionally, (iii) a polymerase II (pol II) construct comprising a pol II promoter operably linked to a coding region and/or a polymerase III (pol III) construct comprising a pol III promoter operably linked to a coding region, as well as a system comprising such an adenoviral vector and a cell line that complements the adenoviral vector, and related systems and methods.
摘要:
The present invention provides methods of detecting and/or characterizing the viral vector particle content of a medium. A medium is provided and contacted with an excitation energy such that, if a viral vector particle is in the medium, an electron associated with the intrinsically fluorogenic portion of the viral vector particle will be raised to an excited energy state. The excited electron is permitted to emit radiation having an emission wavelength which is detected. The viral vector particle content of the medium then can be evaluated by comparing the detected emission wavelength with a standard signal. For example, the number of viral vector particles in a medium can be quantified by comparing the detected wavelength and its corresponding intensity to a standard signal. Similar methods for evaluating the adenoviral vector particle content of a medium and the intrinsically fluorogenic adenoviral structural protein content of a medium are provided. The invention further provides related methods for evaluating the structurally modified viral vector particle content of a medium and evaluating viral vector particle interactions in a medium.
摘要:
An adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a radiation inducible promoter operably linked to the nucleic acid sequence coding for TNF. This invention also provides an adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a spacer element of at least 15 base pairs in the E4 region of the adenoviral genome. A method of producing an adenoviral vector and a method of treating a tumor or cancer in a host comprising administering an anti-cancer or anti-tumor effective amount of the adenoviral vector of the present invention also is provided.