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US 2025/0043282 A1Published application
Attenuated orthomyxovirus-based vector platform
AssigneeNew York University
InventorBenjamin tenOever
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AssigneeNew York University
InventorBenjamin tenOever
Estimating the term…
The present application provides an attenuated orthomyxovirus-based (e.g., influenza A virus (IAV)-based) replicon vector, which optionally encodes a biological cargo, and in which the one or more envelope glycoprotein transcripts are engineered to comprise one or more miRNA Silencing Elements (MSEs) such that the one or more vector envelope glycoproteins are expressed in a first cell type or species, but are not expressed in a second cell type or species, wherein the introduction of the attenuated replicon vector into the second cell type or species results in a sustained production of the biological cargo in the absence of vector propagation and cell death and/or toxicity. In other aspects, the present application is directed to the attenuated replicon vector production and its use for sustained production of biological cargo in vivo and prevention and treatment of diseases.
A recombinant attenuated orthomyxovirus-based replicon (AOR) vector, wherein the AOR vector comprises vRNA segments collectively encoding, (a) optionally a biological cargo, and (b) orthomyxovirus polypeptides, or functional mutants or derivatives thereof, essential for AOR vector cell entry, cell exit and replication, wherein one or more orthomyxovirus envelope glycoproteins or functional mutants or derivatives thereof may be optionally replaced by one or more heterologous envelope glycoproteins which are capable of mediating AOR vector cell entry and/or exit, wherein one or more of the vRNA segments encoding the one or more orthomyxovirus envelope glycoproteins or functional mutants or derivatives thereof or the one or more heterologous envelope glycoproteins comprise one or more microRNA (miRNA) Silencing Elements (MSEs) such that said one or more orthomyxovirus envelope glycoproteins or functional mutants or derivatives thereof or said one or more heterologous envelope glycoproteins are not expressed or are expressed at a substantially lower level in a first cell type or species, but are expressed in a second cell type or species.
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