Compositions for introducing RNA into cells
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.
1. A composition comprising a single stranded mRNA and a
a lipidoid having the structure of formula (IV):
wherein the variables a, b, p, m, n and R 1 to R 6 are defined as follows:
a is 1 and b is an integer of 2 to 4, or a is an integer of 2 to 4 and b is 1;
p is 1 or 2;
m is 1 and n is 1, m is 2 and n is 0, or m is 2 and n is 1; and
R 1 to R 6 are independently of each other selected from: hydrogen; —CH 2 —CH(OH)—R 7 , —CH(R 7 )—CH 2 —OH, —CH 2 —CH 2 —(C═O)—NH—R 7 and —CH 2 —R 7 , wherein R 7 is selected from C3-C18 alkyl and C3-C18 alkenyl having one C—C double bond; a protecting group for an amino group; —C(NH)—NH 2 ; a poly(ethylene glycol) chain; and a receptor ligand; provided that at least two of R 1 to R 6 are —CH 2 —CH(OH)—R 7 , —CH(R 7 )—CH 2 —OH, —CH 2 —CH 2 —(C═O)—NH—R 7 or —CH 2 —R 7 and one of R 1 , R 2 , R 5 , and R 6 is hydrogen, wherein R 7 is selected from C3-C18 alkyl and C3-C18 alkenyl having one C—C double bond; and wherein one or more nitrogen atoms may be protonated.
2. The composition of claim 1 , comprising the single stranded mRNA and the lipidoid having the structure of formula (IVa):
R 1 —NR 2 {CH 2 —(CH 2 ) a —NR 3 —CH 2 —(CH 2 ) b —NR 4 } m —[CH 2 —(CH 2 ) a —NR 5 ] n —R 6 (IVa),
wherein a, b, m, n, and R 1 to R 6 are defined as in claim 1 .
3. The composition of claim 1 , wherein n is 1.
4. The composition of claim 1 , wherein m is 1 and n is 1.
5. The composition of claim 1 , wherein a is 1 and b is 2 or a is 2 and b is 1.
6. The composition of claim 1 , which is in lyophilized form.
7. The composition of claim 6 , which further comprises a lyoprotectant.
8. The composition of claim 7 , wherein the lyoprotectant is at least one of trehalose, sucrose and lactose.
9. A pharmaceutical composition comprising the composition of claim 1 .
10. A method for delivering single stranded mRNA to a target cell or tissue comprising the step of bringing the composition of claim 1 into contact with the target cell or tissue.
11. The composition of claim 1 , wherein the lipidoid forms a complex with the single stranded mRNA.
12. The composition of claim 1 , wherein
a is 1 and b is 2 or 3, or a is 2 and b is 1;
p is 1; and
m is 1 and n is 1.
13. The composition of claim 1 , wherein the composition has a positive zeta potential.
14. The composition of claim 13 , wherein the composition has an N/P ratio of 3 to 60.
15. The composition of claim 13 , wherein the composition has an N/P ratio of 4 to 44.
16. The composition of claim 13 , wherein the composition has an N/P ratio of 2 to 10.
17. The composition of claim 1 , wherein the composition does not comprise siRNA.
18. The composition of claim 7 , wherein the lyoprotectant is lactose.
19. A particle comprising the composition of claim 1 , wherein the particle diameter ranges from 10 to 500 nm.
20. A particle comprising the composition of claim 1 , wherein the particle diameter ranges from 20 to 150 nm.
21. The composition of claim 1 , wherein at least two of the R 1 to R 6 are —CH 2 —CH(OH)—R 7 or —CH(R 7 )—CH 2 —OH.
22. The composition of claim 13 , wherein the composition has an N/P ratio of 8 to 20.
23. The composition of claim 7 , wherein five of R 1 to R 6 are —CH 2 —CH(OH)—R 7 or —CH(R 7 )—CH 2 —OH, wherein R 7 is C8-C16 alkyl or C8-C16 alkenyl having one C—C double bond.