摘要:
The present invention provides, among other things, a method of inhibiting an immune response to a recombinant vector, such as a viral vector, specifically an adenoviral vector. The method comprises contacting a cell with (i) a recombinant vector, preferably a viral vector, most preferably an adenoviral vector, comprising a transgene and (ii) a means of inhibiting an immune response to the recombinant vector selected from the group consisting of a TNF receptor fusion protein, a Fas receptor fusion protein, an IFN receptor fusion protein, a gene encoding a TNF receptor fusion protein, a gene encoding a Fas receptor fusion protein, and a gene encoding an IFN receptor fusion protein, whereupon an immune response to the recombinant vector is inhibited. In this regard, the present invention also provides a recombinant vector and a composition for use in the method.
摘要:
The invention provides an adenoviral vector comprising (a) at least a portion of an adenoviral genome comprising a major late transcription unit containing a terminal exon, wherein the terminal exon comprises a 5′ splice acceptor DNA sequence element and a 3′ polyadenylation signal sequence, and (b) a non-native nucleic acid sequence encoding a protein that does not contribute to the adenoviral vector entry into a host cell, wherein the non-native nucleic acid sequence is positioned within the terminal exon, such that the non-native nucleic acid sequence is selectively expressed in cells within which the adenoviral vector can replicate. The invention further provides an adenoviral vector composition and a method for treating or preventing a pathologic state in a mammal, comprising administering to the mammal the adenoviral vector composition of the invention in an amount sufficient to treat or prevent the pathologic state in the mammal.
摘要:
A method of producing a replication deficient adenovirus comprising a passenger gene and a deficiency in an essential gene function of the E1 region of an adenovirus comprising producing the adenovirus in a cell that provides in trans gene functions of the E1 and E4 regions of one or more adenoviruses not belonging to the same serogroup as the replication deficient adenovirus.
摘要:
The invention provides an expression construct comprising a nucleic acid sequence encoding an adeno-associated virus integration efficiency element (AAV IEE), wherein the expression construct is substantially devoid of AAV inverted terminal repeats (AAV ITRs). Such an expression construct site-specifically integrates into a host cell chromosome when provided to a host cell in conjunction with an AAV Rep protein. The invention also provides a method of integrating a nucleic acid sequence of interest into a host cell chromosome through use of such an expression construct, as well as a method of prophylactically or therapeutically treating a mammal for a pathologic state comprising administering to a mammal such an expression construct comprising a nucleic acid sequence encoding a therapeutic factor.
摘要:
The present invention provides replication-deficient non-group C adenoviral vectors. Also provided is a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such vectors incorporating a foreign nucleic acid.
摘要:
The invention is directed to an adenoviral vector comprising (a) at least one insertion site for cloning a heterologous gene, and, in an orientation opposite to the direction of transcription of the adenoviral region into which it is inserted, (b) a heterologous promoter positioned upstream from the insertion site, (c) a eukaryotic splice acceptor and splice donor site positioned between the promoter and the insertion site; and (c) a polyadenylation sequence positioned downstream of the insertion site. The invention also provides a host cell infected with such a vector, a method of producing a selected protein, and a method of delivering a heterologous gene to an animal heart.
摘要:
The present invention provides an adenoviral gene transfer vector comprising a first fiber gene and a second fiber gene, wherein the fiber genes are different. The present invention also provides related recombinant adenoviral gene transfer vectors and methods of propagating an adenovirus with a fiber protein that does not bind to a native adenoviral fiber receptor.