Abstract: The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one chemical modification.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of PMP22 RNA in a cell or animal, and in certain instances reducing the amount of PMP22 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include demyelination, progressive axonal damage and/or loss, weakness and wasting of foot and lower leg muscles, foot deformities, and weakness and atrophy in the hands. Such neurodegenerative diseases include Charcot-Marie-Tooth disease.

Abstract: The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.

Abstract: The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside.

Abstract: The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having one or more chirally enriched phosphorothioate intemucleoside linkages. In certain embodiments, the modified oligonucleotide decreases expression of target mRNA.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: The present invention provides gapped oligomeric compounds comprising from 1 to about 3 internucleoside linkages having one of formulas I to XVI. In certain embodiments, inclusion of from 1 to about 3 internucleoside linkages of one of formulas I to XVI, improves selectivity for a target RNA relative to an off target RNA. In certain embodiments, the improved selectivity also provides an improved toxicity profile. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount of activity or expression of the target nucleic acid in a cell.

Abstract: Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the gomeric compounds are conjugated to N-Acetylgalactosamine or to N-Acetylgalactosamine anaologues.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.

Abstract: Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the gomeric compounds are conjugated to N-Acetylgalactosamine or to N-Acetylgalactosamine analogues.

Abstract: Provided herein are methods for removal of monomethoxytrityl groups from oligomeric compounds comprising terminally linked monomethoxytrityl protected amino groups. The present methods differ from standard methods for 5?-dimethoxytrityl removal from oligonucleotides in that the present methods are performed at elevated temperatures and higher pH. In certain embodiments, the present methods provide detritylated oligomeric compounds having a reduced percentage of depurination relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide an increased rate of detritylation compared to standard methods. In certain embodiments, the modification of the final detritylation step results in an improved yield.

Abstract: Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.