Lentiviral vectors containing an MHC class I, MHC class II, or B2 microglobulin upstream promoter sequence
Inventors
Bauche, Cecile • SARRY, Emeline
Assignees
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Publication Number
US-9657311-B2
Publication Date
2017-05-23
Expiration Date
Abstract
The present invention relates to the insertion of an MHC class I, MHC Class II, or β2 microglobulin upstream promoter sequence into a lentiviral vector to increase viral titers. The invention encompasses these vectors, methods of making the vectors, and methods of using them, including medicinal uses.
Core Innovation
The invention relates to lentiviral vectors for expressing transgenes under the control of an MHC class I or b22 microglobulin (b22m) promoter. It provides lentiviral expression vectors that include an upstream promoter sequence derived from an MHC class I, MHC class II, or b22 microglobulin source, positioned as part of the lentiviral vector for use with an MHC class I or b22m promoter controlling a transgene.
In the described scope, the lentiviral vector comprises 300-1100 nucleotides of an upstream promoter segment selected from b22m upstream promoter, HLA-A2 upstream promoter, HLA-B7 upstream promoter, HLA-E upstream promoter, or HLA-DRb1 upstream promoter. Orientation and positioning are described as affecting observed outcomes, with comparisons between correctly positioned and oriented segments versus reversed or relocated segments.
The invention is described as increasing viral titers by inserting an MHC class I/II or b22m upstream promoter sequence upstream of the MHC class I or b22m promoter, while aiming to avoid enhancer-driven insertional mutagenesis. It also relates to antigen expression under the MHC class I or b22m promoter using transgenes encoding immunogenic polypeptides or epitopes.
The description further mentions CTL (CD8+) and CD4 immune responses in association with expression of such transgenes under the MHC class I or b22m promoter. The invention is framed for medicaments, vaccines, and therapeutic compositions using the lentiviral vectors.
Claims Coverage
The document identifies one independent claim for a lentiviral expression vector, with dependent claims refining specific upstream promoter identities, segment lengths, orientation, host-cell and producing-method aspects. The independent claim contains two main inventive features.
Upstream promoter segment (MHC/HLA/b22m) in a lentiviral expression vector
A lentiviral expression vector comprising 300-1100 nucleotides of an MHC class I, MHC Class II, or b2 microglobulin upstream promoter sequence, selected from the group consisting of a b2 microglobulin upstream promoter sequence, an HLA-A2 upstream promoter sequence, HLA-B7 upstream promoter sequence, an HLA-E upstream promoter sequence and an HLA-DRb1 upstream promoter sequence.
Transgene controlled by an MHC class I or b22m promoter
A transgene sequence under control of an MHC class I or b2 microglobulin promoter in the lentiviral expression vector, wherein the vector further comprises the defined MHC class I, MHC Class II, or b2 microglobulin upstream promoter sequence.
The claim coverage focuses on lentiviral expression vectors that combine a defined upstream promoter segment from b22m/HLA-A2/HLA-B7/HLA-E/HLA-DRb1 with a transgene positioned under an MHC class I or b22m promoter, using the specified 300-1100 nucleotide segment range.
Stated Advantages
Increases viral titers of lentiviral vectors by inserting an MHC class I/II or b2 microglobulin upstream promoter sequence upstream of an MHC class I or b22m promoter.
Aims to avoid enhancer-driven insertional mutagenesis.
Documented Applications
Medicinal use, including medicaments and vaccines, using the described lentiviral vectors.
Therapeutic compositions using the described lentiviral vectors.
Immune response applications involving antigen expression and CTL (CD8+) and CD4 immune responses using transgenes encoding immunogenic polypeptides or epitopes.
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