In vitro and in vivo intracellular delivery of sirna via self-assembled nanopieces

Patent metadata

Field	Value
Publication number	US-2024156853-A1
Application number	US-202318316693-A
Country	US
Kind code	A1
Filing date	May 12, 2023
Priority date	Mar 26, 2018
Publication date	May 16, 2024
Grant date	—

Abstract

The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.

First claim

1 - 25 . (canceled)

26 . A method of treating a joint disease comprising administration of an effective amount of a rosette nanopiece, wherein said nanopiece comprises i) a compound of Formula I or Formula II,

or a salt thereof, or a combination thereof, and
ii) a nucleic acid.

27 . The method of claim 26 , wherein said joint disease comprises a TNF-α-mediated autoimmune disease.

28 . (canceled)

29 . The method of claim 26 , wherein said nanopiece comprises a TNF-α siRNA.

30 . The method of claim 26 , wherein said nanopiece enters a macrophage cell.

31 . The method of claim 26 , wherein said nanopiece is administered systemically.

32 . (canceled)

33 . The method of claim 26 , wherein said joint disease comprises autoimmune, degenerative, inflammatory, infectious, cancerous, viral, fungal, injured, trauma, genetic, trauma, mechanical, nutritional or mal-alignment derived.

34 . The method of claim 26 , wherein said joint disease comprises osteoarthritis, juvenile onset of rheumatoid arthritis (JRA), reactive arthritis (RA), septic arthritis, tendinitis, or herniation.

35 - 45 . (canceled)

46 . The method of claim 26 ,

wherein, X is CH or N;
R 1 is hydrogen or aliphatic;
R 2 is hydrogen or a linker group; and
Y is absent when R 2 is hydrogen or is an amino acid side chain, amino acid or polypeptide.

47 - 49 . (canceled)

50 . The method of claim 26 , wherein the nucleic acid comprises siRNA.

51 . (canceled)

52 . The method of claim 50 , wherein the nucleic acid comprises the sequence: AAG CCT GTA GCC CAC GTC GTA (SEQ ID NO: 229) and GGC ACC ACT AGT TGG TTG TCT TTG (SEQ ID NO: 230).

53 - 54 . (canceled)

55 . The method of claim 26 , wherein the nucleic acid is anti-miR-181a.

56 . The method of claim 55 , wherein the anti-miR-181a nucleic acid sequence comprises SEQ ID NO: 228 or SEQ ID NO: 229.

57 . The method of claim 26 , wherein the joint disease comprises a cancer in a joint.

58 . The method of claim 57 , wherein the cancer is sarcoma, hemangiopericytoma, connective tissue neoplasm, chondroma, or chondrosarcoma.

Assignees

• Rhode Island Hospital

Inventors

• Chen Qian
• Chen Yupeng
• Yu Hongchuan

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N2310/11

  Antisense · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• A61K31/713 Primary

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title