The present invention provides methods and compositions for reducing lactate production and increasing polypeptide production in cultured cells. In one aspect, the invention provides a method comprising culturing cells expressing a) a small interfering RNA (siRNA) specific for a lactate dehydrogenase (LDH) and b) an siRNA specific for a pyruvate dehydrogenase kinase (PDHK). In another aspect, the invention provides cultured cells or vectors comprising an siRNA specific for a LDH and an siRNA specific for a PDHK.

Disclosed herein are methods of controlling insect pests which infest crop plants, in particular Spodoptera frugiperda (fall armyworm), Lygus hesperus (western tarnished plant bug), Euschistus heros (neotropical brown stink bug), and Plutella xylostella (diamondback moth), and methods of providing plants resistant to such pests. Also disclosed are polynucleotides and recombinant DNA molecules and constructs useful in such methods, insecticidal compositions such as topical sprays containing insecticidal double-stranded RNAs, and plants with improved resistance to infestation by these insects. Further disclosed are methods of selecting target genes for RNAi-mediated silencing and control of these insect pests.

Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule using an RNA-guided DNA endonuclease comprising at least one RNA sequence and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro or using a cassette containing a single repeat-spacer-repeat unit.

Methods for producing reassortant viruses are provided wherein the transcription and/or translation of the hemagglutinin and/or neuraminidase genes are suppressed.

An affinity substrate for the selective binding of a protein of blood plasma includes a solid substrate material on which are immobilized deoxyribonucleic aptamers specifically binding with the plasma protein.

Aspects of the disclosure relate to particle formulations, e.g., nanoparticle formulations, methods of making particle formulations, and methods for delivery of oligonucleotides and/or synthetic RNA, e.g., for increasing gene expression in a targeted manner. In some embodiments, compositions and methods are provided that are useful for posttranscriptionally altering protein and/or RNA levels in a targeted manner. Aspects of the disclosure described herein provide compositions and methods that are useful for protecting RNAs from degradation (e.g., exonuclease mediated degradation).

The present invention pertains to the use of miRNA technology for improving recombinant production of polypeptides of interest in host cells. Expression cassettes are provided which produce a miRNA targeting and down-regulating a host cell protein which interferes with production of the polypeptide of interest.

Aspects of the disclosure relate to particle formulations, e.g., nanoparticle formulations, methods of making particle formulations, and methods for delivery of oligonucleotides and/or synthetic RNA, e.g., for increasing gene expression in a targeted manner. In some embodiments, compositions and methods are provided that are useful for posttranscriptionally altering protein and/or RNA levels in a targeted manner. Aspects of the disclosure described herein provide compositions and methods that are useful for protecting RNAs from degradation (e.g., exonuclease mediated degradation).