The invention provides methods and compositions for improved production of large quantities of unencapsidated double strand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phosporibosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of modulatory polynucleotides.

An isolated RNA molecule includes an artificial microRNA precursor comprising in the 5′.fwdarw.3′ direction: a first terminal oligonucleotide consisting of AGGCCR (SEQ ID NO: 1) or a nucleotide sequence in which one to three nucleotides in SEQ ID NO: 1 are substituted; a passenger strand oligonucleotide; a first central oligonucleotide consisting of CYG (SEQ ID NO: 2); a second central oligonucleotide consisting of a nucleotide sequence having at least 70% homology with UUGAAUAKAAAU (SEQ ID NO: 3); a third central oligonucleotide consisting of YGG (SEQ ID NO: 4); a guide strand oligonucleotide; and a second terminal oligonucleotide consisting of UGGAYYK (SEQ ID NO: 5) or a nucleotide sequence in which one to three nucleotides in SEQ ID NO: 5 are substituted.

The invention provides methods and compositions for improved production of large quantities of unencapsidated double strand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phosporibosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA.

The invention provides methods of treating polyglutamine diseases, e.g., spinocerebellar ataxia Type 6, in a subject, comprising administering to the subject an IRES inhibitor in an amount effective for treating the SCA6 in the subject. Also provided herein are the IRES inhibitors, and pharmaceutical compositions comprising the same.

The invention concerns the field of cell culture technology. It concerns RNA having a specific sequence, expression vectors encoding the RNA, production host cell lines comprising the RNA, and methods of producing recombinant biopharmaceutical products using engineered host cell with altered levels of the RNAs, such as small non-coding RNAs, preferably microRNAs (miRNAs). The invention also relates to engineered host cells with altered levels in one or more of the RNAs. Those cell lines have improved secretion and/or growth characteristics in comparison to control cell lines.

The present invention relates to concatemeric RNA molecules, compositions, particles, and methods of uses thereof.

Described herein are compositions and methods for treating a disease in a subject by administering delivery vectors that express artificial microRNAs, artificial microRNA clusters, and/or a combination of microRNA clusters and associated non-coding RNAs to the subject. Also described herein are methods for preparing artificial microRNAs and artificial microRNA clusters.

Provided are methods for editing RNA by introducing a deaminase-recruiting RNA in a host cell for deamination of an adenosine in a target RNA, and deaminase-recruiting RNAs used in the RNA editing methods and compositions comprising the same.

Provided herein are novel .sup.10Fn3 domains which specifically bind to PD-L1, as well as imaging agents based on the same for diagnostics.