Compositions for introducing RNA into cells

Inventors

Dohmen, Christian • Plank, Christian • Rudolph, Carsten • Koch, Christian

Assignees

Ethris GmbH

Abstract

The present invention relates to oligomers, polymers and lipidoids comprising characteristic oligo(alkylene amine) moieties which are useful as vehicles for transfecting a cell with RNA. The present invention furthermore relates to a composition comprising at least a nucleic acid and an oligomer or polymer or a lipidoid comprising such oligo(alkylene amine) moieties and to a method of transfecting a cell using said composition. Furthermore, the present invention relates to pharmaceutical compositions and uses.

Core Innovation

The invention relates to a composition comprising a single stranded mRNA and a lipidoid having the structure of formula (IV). The lipidoid structure is defined by variables a, b, p, m and n and substituents R1 to R6, with constraints on the values of a, b, p, m and n and with one or more nitrogen atoms optionally protonated to provide cationic character. The substituents are selected from hydrogen, substituted aliphatic and hydroxyl-bearing moieties containing an R7 group, protecting groups for an amino group, a C(NH)NH2 moiety, a poly(ethylene glycol) chain, and a receptor ligand.

At least two of R1 to R6 are selected from specific substituent patterns that include 2-carbon linkages bearing hydroxyl and C3–C18 alkyl or C3–C18 alkenyl groups with one C=C double bond. One of R1, R2, R5 and R6 is hydrogen while the remaining patterned substituents are present as specified. These structural features are tied to the ability of the lipidoid to form a complex with the single stranded mRNA.

The document states an unexpected principle for RNA delivery efficacy in which alternating arrangements in groups of three or more units and an ethyleneamine unit provide more efficacious RNA delivery than non-alternating analogs. The disclosed formulations are also described as being adapted for delivery to cells and tissues, and the composition can further be limited to not include siRNA, with optional lyoprotectants in a lyophilized form and trehalose identified as a preferred lyoprotectant.

Claims Coverage

The claim coverage centers on a composition that includes single stranded mRNA combined with a lipidoid of formula (IV). One independent claim is provided, and the coverage includes structural constraints on the lipidoid, lipidoid–mRNA complex formation, and dependent limitations such as positive zeta potential, an N/P ratio ranging from 4 to 44, and exclusion of siRNA.

Overall, the claim set is centered on a composition that pairs single stranded mRNA with a defined formula (IV) lipidoid having specified structural substituent rules and optional protonation. Dependent features further narrow coverage to lipidoid–mRNA complex formation and to measured formulation constraints such as positive zeta potential and an N/P ratio range, while also providing an explicit exclusion of siRNA.

Stated Advantages

Documented Applications