Haematopoietic stem cell treatment

Patent metadata

Field	Value
Publication number	US-12589115-B2
Application number	US-201917042008-A
Country	US
Kind code	B2
Filing date	Mar 29, 2019
Priority date	Mar 29, 2018
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

The present invention relates to modified haematopoietic stem cells, methods for preparing them, and their use in therapy; as well as methods and reagents for expanding haematopoietic stem cells (HSC) and methods for treating haematological disorders. A particular aspect relates to a method for treating a disease or condition characterised by elevated YTHDF2 expression comprising administering to a patient an effective amount of an YTHDF2 inhibitor. Certain aspects of the invention rely on YTFIDF2 protein level or function and use of YTFIDF2 inhibitors.

First claim

The invention claimed is:

1 . A method for treating a hematological cancer in a patient in need thereof, comprising administering to the patient an effective amount of an YTHDF2 (YTH domain family 2) inhibitor, wherein the YTHDF2 inhibitor is a nucleic acid based inhibitor molecule selected from the group consisting of a small interfering RNA interference molecule (RNAi), an antisense oligonucleotide (ASO), and a nucleic acid aptamer.

2 . The method according to claim 1 , wherein the hematological cancer is selected from the group consisting of: acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL).

3 . The method according to claim 1 , wherein the cancer cells express increased levels of YTHDF2 mRNA or YTHDF2 protein relative to normal cells.

4 . The method according to claim 1 , wherein the nucleic acid based inhibitor molecule is a small interfering RNA interference molecule (RNAi).

5 . The method according to claim 1 , wherein the amount of the YTHDF2 inhibitor is effective to reduce YTHDF2 protein level, YTHDF2 function, YTHDF2 interactions with the CCR4-NOT complex or YTHDF2 interaction with m6A mRNA in a cell.

6 . The method according to claim 1 , wherein the YTHDF2 inhibitor is administered before, during or after chemotherapy.

7 . The method according to claim 1 , wherein the nucleic acid based inhibitor molecule is an antisense oligonucleotides (ASO).

Assignees

• Univ Court Univ Of Edinburgh

Inventors

• Kranc Kamil Romuald
• O'Carroll Dónal

Classifications

• C12N2310/16

  Aptamers · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · 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

• C12N9/22

  Ribonucleases {[RNase]; Deoxyribonucleases [DNase]} · CPC title

• A61P35/02

  specific for leukemia · CPC title