Abstract: This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting Hepatitis B virus in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of an HBV genome.

Abstract: Disclosed herein is a compound of Formula I, wherein R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof.

Abstract: This invention provides a range of translatable messenger UNA (mUNA) molecules. The mUNA molecules can be translated in vitro and in vivo to provide an active polypeptide or protein, or to provide an immunization agent or vaccine component. The mUNA molecules can be used as an active agent to express an active polypeptide or protein in cells or subjects. Among other things, the mUNA molecules are useful in methods for treating rare diseases.

Abstract: Disclosed herein is a lipid composition comprising a compound having the formula IA, or a pharmaceutically acceptable salt thereof, wherein R3 is a linear or branched alkylene of 1-6 carbons; R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1-6 carbons; and L3 is a bond or an alkane of 1-6 carbons.

Abstract: A single stranded oligonucleotide containing two or more acyl-amino-LNA or hydrocarbyl-amino-LNA nucleotide monomers, in which other nucleotide monomers can be DNA, RNA or chemically modified nucleotide monomers; in which the monomers of the oligonucleotide are linked by phosphodiester linkages and/or phosophorothioate linkages and/or phosphotriester linkages, in which the acyl and hydrocarbyl groups of the acyl-amino-LNA and hydrocarbyl-amino-LNA monomers are optionally substituted and thus optionally contain one or more hydroxyl group(s), amino group(s), thio group(s), oxo group(s), alkylthio group(s), ether group(s), and/or thiol (mercapto) group(s), and in which the acyl and hydrocarbyl groups of the acyl-amino-LNA and hydrocarbyl-amino-LNA monomers are linear or branched chains, cyclic or a combination of both, provided that the total number of carbon atoms in each acyl and hydrocarbyl group is less than 30.

Abstract: This invention provides UNA oligomers for gene silencing with reduced off-target effects. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and various nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis with reduced off-target effects by administering a UNA oligomer to a subject.

Abstract: This invention provides pharmaceutical compositions containing a UNA oligomer targeted to TTR and a pharmaceutically acceptable carrier. The compositions can be used in methods for treating or preventing TTR-related amyloidosis in a primate. The compositions, upon administering a single dose to the primate, can reduce TTR protein in the primate for a period of days to weeks.

Abstract: What is described is a compound of formula III or IV wherein R1 is a branched alkyl with 12 to 20 carbons; R2 is a linear alkyl with 5 to 10 carbons or a branched alkyl with 12 to 20 carbons; L1 and L2 are each a bond or a linear alkylene having 1 to 3 carbon atoms, when L3 is a bond; L1 and L2 are each a linear alkylene or alkenylene 5 to 18 carbon atoms, when L3 is an alkylene of 5 to 18 carbons; X is S or O; R3 is of a lower alkyl; and R4 and R5 are the same or different, each a lower alkyl; or a pharmaceutically acceptable salt thereof.

Abstract: What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract: This invention provides UNA oligomers for regulating the expression of a target gene. The UNA oligomers contain UNA monomer linkers, and may contain one or more nucleotides modified with a 2?-O-methyl group, one or more nucleotides modified with a 2?-deoxy-2?-fluoro group, and one or more phosphorothioate or chiral phosphorothioate intermonomer linkages. UNA oligomers can be used as active agents for preventing or treating disease.

Abstract: What is described is a trinucleotide cap analog comprising m7G(5?)p3-N1pN2 for increased efficiency of in vitro transcription of m7G(5?)p3-RNA, wherein m7G is N7-methylguanosine or analog, (5?)p3 is a 5?,5?-triphosphate bridge, and N1 or N2 or both ribonucleotide analogs linked to each other by a phosphate, p, and wherein the trinucleotide cap analog increases the efficiency of in vitro transcription.

Abstract: This invention provides UNA oligomers for therapeutics having prolonged stability. The UNA oligomers can be composed of one or more 2?-3?-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their activity.

Abstract: This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting expression of a TTR gene in a subject. The compounds have a first strand and a second strand, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of a TTR gene.

Abstract: What is described herein are cationic lipids that facilitate the intracellular delivery of biologically active molecules, comprising a compound of formula I wherein R1 is a linear alkyl, alkenyl, or alkynyl of 2 to 12 carbons, or a branched alkyl with 7-25 R2 is a branched alkenyl with 7-25 carbons, L1 and L2 are independently a linear alkenylene with 2-18 carbons, X is S or O, L3 is a bond, and R3 R4, and R5 are each a linear or branched alkylene with 1-6 carbons.

Abstract: What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract: This invention encompasses compounds, structures, compositions and methods for therapeutic guide molecules that direct CRISPR gene editing. A guide molecule for directing gene editing can be allele selective, or disease allele selective, and can exhibit reduced off target activity. A guide molecule can be composed of monomers, including UNA monomers, nucleic acid monomers, and modified nucleotides, wherein the compound is targeted to a genomic DNA. The guide molecules of this invention can be used as active ingredients for editing or disrupting a gene in vitro, ex vivo, or in vivo.

Abstract: What is described is a compound of formula I wherein X is an alkylene or an alkenylene; Y is a monocyclic, bicyclic, or tricyclic arene or heteroarene; Z is S or O; L is a linear or branched alkylene of 1 to 6 carbons; R1 is a branched alkyl or alkenyl of 1 to 25 carbons; R2 is a alkyl or alkenyl of 1 to 20 carbons; R3 and R4 are independently a linear or branched alkyl of 1 to 6 carbons; n is 0 to 6; and m, p, q, and r are independently 1-18; or a pharmaceutically acceptable salt thereof.

Abstract: What is described is a compound wherein R1 and R2 are the same or different, each a linear or branched alkyl consisting of 1 to 20 carbons, or a linear or branched alkenyl or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a bond, a linear alkylene of 1-18 carbons, or a linear alkenylene consisting of 2 to 18 carbons; L3 is a bond or a linear or branched alkylene consisting of 1 to 6 carbons; L4 is a bond or a methylene; X is S or O, R3 is a linear or branched alkylene consisting of 1 to 6 carbons, and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract: This invention provides UNA oligomers for selectively inhibiting V30M TTR expression, which can be used in treating amyloidosis. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis by administering a UNA oligomer to a subject.

Abstract: Described herein is a compound having the structure of formula I, II, or III, wherein R comprises a double stranded RNA molecule, and L1, L2, and L3 independently for each occurrence comprise a ligand selected from the group consisting of a carbohydrate, a cholesteryl, or a peptide; a pharmaceutically accepted salt or pharmaceutical composition thereof; and a method of making the compound.