Provided herein are methods of administering gapmer oligomeric compounds with GalNAc conjugate groups to a human.

A medicament can include a product for in vivo expression of a protein in a living being. The product can include a first entity, which includes a nucleic acid encoding an intracellularly expressible protein, and an associated second entity configured for specific binding to a cellular structure of the living being. One example of the product is a nucleotide-modified mRNA, in which includes a first ribonucleotide sequence encoding the intracellularly expressible protein, and a second ribonucleotide sequence encoding an aptamer configured for specific binding to the cellular structure of the living being.

The invention relates to oligonucleotides for inducing skipping of exon 55 of the dystrophin gene. The invention also relates to methods of inducing exon 55 skipping using the oligonucleotides.

Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

A method of treating a developmental syndrome in a patient in need thereof includes applying ultrasound to a target location in the patient's brain to enhance permeability of the patient's blood brain barrier at the target location and administering to the patient a vector encoding BDNF for delivery of BDNF to the target location, wherein the method provides improvement in at least one symptom of the developmental syndrome. Also provided is a method of treating a developmental syndrome in a patient in need thereof that includes administering to the patient an effective amount of a vector including (i) a constitutive promoter operatively linked to nucleic acid encoding BDNF, and (ii) a regulatory sequence including an AGRP promoter operatively linked to an interference RNA sequence, wherein the regulatory sequence down regulates expression of BDNF in response to BDNF induced physiological changes, and the method provides improvement in at least one symptom of the developmental syndrome.

An isolated nucleic acid molecule encoding a variant of sirtuin 6 (SIRT6) having at least 75% identity with sequence SEQ ID NO: 1, the variant having at least one mutation selected from a N308K substitution and a A313S substitution with respect to sequence SEQ ID NO: 1. Also, means for the regulation of ageing, and/or senescence, and/or lifespan in an individual. Further, means for the repair of double strand breaks in a cell. Finally, means for the prevention and/or the treatment of an age-related disease.

Compositions of polynucleotide(s), pharmaceutical compositions thereof, and methods of use thereof are disclosed. A polynucleotide may encode for a cystic fibrosis transmembrane conductance regulator (CFTR) protein or a functional fragment thereof. The polynucleotide may be assembled with a lipid composition for targeted delivery to a cell or an organ, such as a lung cell or a lung of a subject. Methods for enhancing an expression or activity of CFTR protein in a cell are provided. Methods for treating a subject having or suspected of having a CFTR-associated condition are also provided.

The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.

Provided herein are lyophilized compositions comprising a capsid-free closed ended DNA (ceDNA) vector comprising at least one nucleic acid sequence between flanking inverted terminal (ITRs), wherein the at least one nucleic acid sequence encodes a therapeutic protein, and uses thereof.

Disclosed herein are therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use.