Abstract: 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.

Abstract: Disclosed herein are methods and compositions for preventing pain induction, interrupting pain signaling stemming from various insults, or alleviating pain perception in a subject.

Abstract: The present application provides an RNA-based system for generating a virus of the Orthomyxoviridae family, and methods of producing viruses of the Orthomyxoviridae family using such system.

Abstract: The invention is directed to novel live attenuated influenza virus (LAIV) vaccines comprising one or more microRNA (miRNA) Response Element(s) (MRE) within an influenza virus genome. The MREs useful for the present invention can be derived from any miRNA which is highly expressed in influenza-targeted cells of an animal in need of vaccination but are not expressed or are expressed at very low levels in species (e.g., embryonated chicken eggs) or cell lines used for a large-scale vaccine production. This allows efficient vaccine production but renders the vaccine virus susceptible to attenuation in the influenza-targeted cells of vaccinated animals expressing a cognate miRNA.

Abstract: The invention is directed to novel live attenuated influenza virus (LAIV) vaccines comprising one or more microRNA (miRNA) Response Element(s) (MRE) within an influenza virus genome. The MREs useful for the present invention can be derived from any miRNA which is highly expressed in influenza-targeted cells of an animal in need of vaccination but are not expressed or are expressed at very low levels in species (e.g., embryonated chicken eggs) or cell lines used for a large-scale vaccine production. This allows efficient vaccine production but renders the vaccine virus susceptible to attenuation in the influenza-targeted cells of vaccinated animals expressing a cognate miRNA.