US 11,701,379 B2
In vitro and in vivo intracellular delivery of siRNA via self-assembled nanopieces
Qian Chen, Barrington, RI (US); Yupeng Chen, Sharon, MA (US); and Hongchuan Yu, Chestnut Hill, MA (US)
Assigned to Rhode Island Hospital, Providence, RI (US)
Appl. No. 17/41,399
Filed by Rhode Island Hospital, Providence, RI (US)
PCT Filed Mar. 26, 2019, PCT No. PCT/US2019/024155
§ 371(c)(1), (2) Date Sep. 24, 2020,
PCT Pub. No. WO2019/191151, PCT Pub. Date Oct. 3, 2019.
Claims priority of provisional application 62/648,233, filed on Mar. 26, 2018.
Prior Publication US 2021/0023117 A1, Jan. 28, 2021
Int. Cl. C07H 21/02 (2006.01); C07H 21/04 (2006.01); A61K 31/713 (2006.01); A61K 47/54 (2017.01); A61K 47/69 (2017.01); A61P 19/02 (2006.01); C12N 15/113 (2010.01)
CPC A61K 31/713 (2013.01) [A61K 47/545 (2017.08); A61K 47/6929 (2017.08); A61K 47/6949 (2017.08); A61P 19/02 (2018.01); C12N 15/1136 (2013.01); C12N 2310/141 (2013.01); C12N 2320/31 (2013.01)] 2 Claims
 
1. A method of treating rheumatoid arthritis comprising the systemic administration of an effective amount of a rosette nanopiece and a nucleic acid, wherein said nanopiece comprises a compound of Formula I or Formula II,

OG Complex Work Unit Chemistry
or a salt thereof,
wherein,
X is CH or N;
R2 is hydrogen or a linker group;
Y is absent when R2 is hydrogen or is an amino acid or polypeptide;
R1 is hydrogen or aliphatic,
wherein the amino acid side chain is selected from:

OG Complex Work Unit Chemistry
wherein, the compounds of Formula (I), Formula (II), or a salt thereof, or a combination of Formula (I) and Formula (II) self-assemble to form a nanotube, and
wherein the nucleic acid comprises an siRNA selected from the group consisting of TNF-α siRNA, a sequence comprising AAG CCT GTA GCC CAC GTC GTA (SEQ ID NO: 229), a sequence comprising GGC ACC ACT AGT TGG TTG TCT TTG (SEQ ID NO: 230), an anti-miR-181a comprising SEQ ID NO: 228, and an anti-miR-181a comprising SEQ ID NO: 229.