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: What is described is a method of synthesis of the compound of formula 1A, or a salt thereof, wherein R3 is a linear or branched alkene of 1, 2, 3, 4, 5 or 6 carbons; R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons; and L3 is a bond or an alkane of 1, 2, 3, 4, 5 or 6 carbons.

Abstract: Here described is a method of delivery of a drug to a stellate cell using a composition comprising a compound of formula I: wherein R1 and R2 are independently selected from C10 to C18 alkyl, C12 to C18 alkenyl, and oleoyl; R3 and R4 are independently selected from C1 to C6 alkyl and C2 to C6 alkanol; X is selected from —CH2—, —S—, and —O—, or X is absent; Y is selected from —(CH2)n, —S(CH2)n—, —O(CH2)n—, -thiophene-, -SO2(CH2)n—, and ester; n=1-4; a=1-4; b=1-4; c=1-4; and Z? is a counterion.

Abstract: What is described is a compound of formula I wherein R1 is a linear alkyl, alkenyl, or alkynyl of 2 to 12 carbons, or a branched alkyl with 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, or 7 carbons, R2 is a branched alkyl with 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, or 7 carbons, L1 and L2 are independently a linear alkylene with 1-18 carbons or alkenylene with 2-18 carbons, X is S or O, L3 is a bond or an alkylene with 1 to 6 carbons, R3 is an alkylene with 1 to 6 carbons, and R4 and R5 are the same or different, each a linear or branched alkyl with 1 to 6 carbons; 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: 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: Here described are compounds consisting of the structure (targeting molecule)m-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including these compounds which are useful for the targeting and delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.

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: 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: 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: Here described are compounds of formula I: wherein R1 and R2 are independently selected from C10 to C18 alkyl, C12 to C18 alkenyl, and oleoyl; R3 and R4 are independently selected from C1 to C6 alkyl and C2 to C6 alkanol; X is selected from —CH2—, —S—, and —O—, or X is absent; Y is selected from —(CH2)n, —S(CH2)n—, —O(CH2)n—, -thiophene-, —SO2(CH2)n—, and ester; n=1-4; a=1-4; b=1-4; c=1-4; and Z? is a counterion. Also described herein are compositions and pharmaceutical formulations including compounds of formula I which are useful for the delivery of therapeutic agents, and methods of using these compositions and formulations.

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.

Abstract: What is described is a compound having the formula wherein R1 is branched alkyl of the structure (CH3(CH2)m)2CH—, wherein m is 2 or 3; R2 is a linear alkyl of 1, 2, 3, 4, 5, 6, 7, 8, or 9 carbons, a branched alkyl of 3, 4, 5, 6, 7, 8, or 9 carbons, or an alkenyl or alkynyl of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbons; R3 is —(CH2)p—, wherein p is 2, 3, 4, 5 or 6; R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons; L1 and L2 are the same or different, of the structure —(CH2)n—, wherein n is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18; L3 is a bond; X1 is —CO—O— whereby -L2-CO—O—R2 is formed; X2 is S or O; and X3 is —CO—O— whereby -L1-CO—O—R1 is formed; and wherein m+n+p is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27; or a pharmaceutically acceptable salt thereof.

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 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 compound having the formula wherein R1 is branched alkyl of the structure (CH3(CH2)m)2CH—, wherein m is 2 or 3; R2 is a linear alkyl of 1, 2, 3, 4, 5, 6, 7, 8, or 9 carbons, a branched alkyl of 3, 4, 5, 6, 7, 8, or 9 carbons, or an alkenyl or alkynyl of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbons; R3 is —(CH2)p—, wherein p is 2, 3, 4, 5 or 6; R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons; L1 and L2 are the same or different, of the structure —(CH2)n—, wherein n is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18; L3 is a bond; X1 is —CO—O— whereby —L1—CO—O—R2 is formed; X2 is S or O; and X3 is —CO—O— whereby —L1—CO—O—R1 is formed; and wherein m+n+p is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27; or a pharmaceutically acceptable salt thereof.

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: 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: What is described is a compound of formula I wherein R1 is a linear alkyl, alkenyl, or alkynyl of 2 to 12 carbons, or a branched alkyl with 12 to 20 carbons, R2 is a branched alkyl with 12 to 20 carbons, L1 and L2 are independently a linear alkylene with 1-18 carbons or alkenylene with 2-18 carbons, X is S or O, L3 is a bond or an alkylene with 1 to 6 carbons, R3 is an alkylene with 1 to 6 carbons, and R4 and R5 are the same or different, each a linear or branched alkyl with 1 to 6 carbons.

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.