Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

Provided herein are PIWI-interacting RNA (piRNA) derived from therapeutic exosomes, and methods of use thereof to treat a condition requiring tissue repair and/or regeneration. Conditions treated by the exosome-derived piRNAs and/or exosomes carrying the same include, in some embodiments, ischemic injury and/or tissue fibrosis. Also provided are therapeutic compositions comprising exosome-derived piRNA and a pharmaceutically acceptable excipient.

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. Also provided are kits for detecting the amount of SMN protein in a sample of cerebrospinal fluid.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an APOE gene, as well as methods of inhibiting expression of an APOE gene and methods of treating subjects having an APOE-associated neurodegenerative disease or disorder, e.g., Alzheimer's disease and Parkinson's disease, using such dsRNAi agents and compositions.

The invention discloses a method for improving immunity in shrimps, by administering a double-stranded RNA specific to tyrosine hydroxylase to a shrimp body to improve immunity of the shrimp body, wherein the double-stranded RNA is administered to the shrimp body by injection into the ventral sinus of the cephalothorax of the shrimp body.

New dosing regimens for treating muscular dystrophy in a patient suffering from Duchenne muscular dystrophy (DMD) with an antisense oligonucleotide conjugate that causes skipping of an exon in the human dystrophin gene are described. Also described is a method of treating a patient with an antisense oligomer CPP conjugate and a magnesium supplement.

The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of treating a subject having a myelin deficiency, may comprise expressing, in glial progenitor cells of the subject, one or more transcription factors selected from the group consisting of B-cell lymphoma/leukemia 11A (BCL11A), histone deacetylase 2 (HDAC2), histone-lysine N-methyltransferase EZH2 (EZH2), myc proto-oncogene protein (MYC), high mobility group protein HMGI-C (HMGA2), nuclear factor 1 B-type (NFIB), and transcriptional enhancer factor TEF-4 10 (TEAD2), wherein said expressing is effective to induce myelination in the subject, thereby treating the myelin deficiency.

Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.

Drug delivery systems and methods are disclosed herein. In some embodiments, a drug delivery system can be configured to deliver a drug to a patient in coordination with a physiological parameter of the patient (e.g., the patient’s natural cerebrospinal fluid (CSF) pulsation or the patient’s heart or respiration rate). In some embodiments, a drug delivery system can be configured to use a combination of infusion and aspiration to control delivery of a drug to a patient. Catheters, controllers, and other components for use in the above systems are also disclosed, as are various methods of using such systems.

The invention relates methods of using RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.