Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.

Provided herein are methods for decreasing LRRK2 mRNA expression. Such methods are useful to ameliorate LRRK2 associated diseases. Such LRRK2 associated diseases include Parkinson's Disease, including non-LRRK2 mediated Parkinson's Disease.

Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

The disclosure provides novel personalized therapies, kits, transmittable forms of information and methods for use in treating patients having cancer, wherein the cancer is amenable to therapeutic treatment with an inhibitor, e.g., an inhibitor of any of the targets disclosed herein. Kits, methods of screening for candidate inhibitors, and associated methods of treatment are also provided.

Provided herein are non-naturally occurring self-assembling polypeptides for transferring nucleic acids and/or proteins to a cell, pharmaceutical compositions comprising such polypeptides, and methods for treatment comprising use of such compositions. The methods for producing polypeptide compositions may include combining in a solution, unassembled recombinant GAG-like proteins, nucleic acids and/or proteins in low salt conditions; and increasing the ionic strength of the solution.

The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the UGT1a1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of UGT1a1.

The present invention provides oligonucleotides comprising 2′-O-methyl (2′-OMe) and 2′-deoxy-2′-fluoro (2′-F) modifications, compositions thereof, and methods of use for reducing the expression or activity of a gene.

The present invention relates to compositions of recombinant polynucleic acid constructs comprising at least one nucleic acid sequence encoding an siRNA capable of binding to a target mRNA and at least one nucleic acid sequence encoding a gene of interest. Also disclosed herein is use of the compositions in treating a disease or a condition and in simultaneously modulating expression of two or more genes.

siRNA compositions are provided that contain gemcitabine (GEM) in place of cytosine moieties within the siRNA sequence. Pharmaceuticals compositions containing these siRNA molecules, and methods of using the compositions for treating diseases such as cancer are provided.

A gene editing system is provided that comprises a first nucleotide molecule encoding a dCas9-Ten-Eleven Translocation methylcytosine dioxygenase 1 catalytic domain (TET1CD) fusion protein; and a second nucleotide molecule encoding at least one small guide RNA (sgRNA), comprising: a scaffold region and a spacer region, wherein the spacer region hybridizes to a nucleotide sequence complementary to a target sequence adjacent to a 5′-end of a protospacer adjacent motif (PAM), and wherein the target sequence and the PAM are located within 1 kilobase (kb) of the transcriptional start site (TSS) of the CDKL5 gene. Methods of making and using the system are further described herein.