Abstract: What is described is a compound of formula I wherein R is a linear alkyl of 1 to 12 carbons, or a linear alkenyl or alkynyl of 2 to 12 carbons; L is a linear alkylene or alkenylene of 5 to 18 carbons; X is —CO—O— or —O—CO—; Y is S or O; R1 is a linear or branched alkylene consisting of 1 to 6 carbons; and R2 and R3 are the same or different, consisting of a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; and n is 1-6; or a salt, a solvate, or a pharmaceutical formulation thereof.

Abstract: What is described is a compound of formula (1) wherein R1 and R2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or an alkenyl or alkynyl with 2 to 11 carbon atoms; L1 and L2 are the same or different, each a linear alkyl having 5 to 18 carbon atoms, or form a heterocycle with N; X1 is a bond, or is —CO—O— whereby L2-CO—O—R2 is formed; X2 is S or O; L3 is a bond or a lower alkyl, or form a heterocycle with N; R3 is 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 lipid particle comprising the compound of formula I wherein R1 consists of alkyl, alkenyl, alkynyl, or cholesteryl; R2 consists of alkyl or alkenyl; L1 consists of alkyl, alkylene or alkenyl; X1 consists of —O—(CO)— or —(CO)—O—; X2 consists of S or O; L2 consists of a bond or alkylene; R3 consists of alkylene; and R4 and R5 are the same or different, each consisting of alkyl; or a pharmaceutical preparation thereof.

Abstract: What are described are compounds of formula II. The compound of formula II consists of a compound in which R1 and R2 are both a linear alkyl consisting of 1 to 12 carbons, an alkenyl or alkynyl consisting of 2 to 12 carbons; L1 and L2 both consist of a linear alkylene or alkenylene consisting of 5 to 18 carbons; X is S; L3 consists of a bond; R3 consists of a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each consisting of 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 wherein R1 consists of a linear or branched alkyl consisting of 1-18 carbons, an alkenyl or alkynyl consisting of 2 to 12 carbons, or a cholesteryl; R2 consists of a linear or branched alkyl or an alkenyl consisting of 1 to 18 carbons; L1 consists of a linear alkyl consisting of 5 to 9 carbons or, when R1 consists of a cholesteryl then L1 consists of a linear alkylene or alkenyl consisting of 3 to 4 carbons; X1 consists of —O—(CO)— or —(CO)—O—; X2 consists of S or O; L2 consists of a bond or a linear alkylene of 1 to 6 carbons; R3 consists of a linear or branched alkylene with 1 to 6 carbons; and R4 and R5 are the same or different, each consisting of a linear or branched alkyl of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract: This disclosure provides double-stranded RNA complexes having one or more hydroxymethyl substituted nucleomonomer(s) in the passenger strand (or sense strand) of an RNA complex. RNA complexes of the disclosure may be useful for therapeutic applications, diagnostic applications or research applications. RNA complexes include short interfering RNA complexes (siRNA) capable of modulating gene expression comprising an antisense strand and a continuous or a discontinuous passenger strand (“sense strand”). Further, one or more hydroxymethyl substituted nucleomonomer(s) of this disclosure may be positioned at the 3?-end, at the 5?-end, at both the 3?-end and 5?end.

Abstract: This invention provides UNA oligomers for therapeutics that can be used to modulate or reduce gene expression. The UNA oligomers can be composed of one or more 2?-3?-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, and can be a duplex having first and second strands. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can provide reduced off target effects while modulating gene expression.

Abstract: This invention provides UNA oligomers for therapeutics that can be used to target micro-RNAs. The UNA oligomers can be composed of one or more 2?-3?-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, and can be a single stranded oligomer. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used to target micro-RNAs to reduce micro-RNA activity.

Abstract: This invention is directed to oligomers composed of 2?-3?-seco-nucleomonomers and nucleotides or modified nucleotides, wherein the oligomer can be a microRNA and include from one to five 2?-3?-seco-nucleomonomers. The oligomers can have a sequence that is complementary to a target nucleotide sequence and be used for affecting the regulation of gene expression. Among other things, the oligomers can provide reduced off target effects.