公开(公告)号：US20170304369A1

公开(公告)日：2017-10-26

申请号：US15517912

申请日：2015-10-08

Applicant: Agency for Science, Technology and Research

Inventor： Lay Teng ANG ,  Kyle M. LOH ,  Bing LIM

IPC: A61K35/407 ,  C12N5/071 ,  C12N5/073 ,  G01N33/00 ,  C12N5/00

CPC classification number: A61K35/407 ,  C12N5/00 ,  C12N5/0603 ,  C12N5/067 ,  C12N5/0672 ,  C12N2500/38 ,  C12N2500/44 ,  C12N2501/00 ,  C12N2501/01 ,  C12N2501/115 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/237 ,  C12N2501/33 ,  C12N2501/385 ,  C12N2501/39 ,  C12N2501/415 ,  C12N2501/42 ,  C12N2501/727 ,  C12N2506/02 ,  G01N33/00

Abstract: The present disclosure provides methods and kits for the differentiation of stem cells into relevant liver cell lineages, as well as methods of using the relevant liver cell lineages in screening for a cellular response, a phenotype and in the treatment of a condition. In one embodiment, stem cells are first differentiated into cells of the definitive endoderm lineage, which are differentiated into posterior foregut (PFG) lineage cells by one or more of retinoic acid activators and/or one or more inhibitors of transforming growth factor-β (TGFβ). An additional embodiment provides a method for the differentiation of posterior foregut lineage cells into liver bud progenitors (LB) by one or more activators of TGFβ signalling, and/or one or more modulators of Wnt signalling, and/or one or more activators of cyclic AMP/PKA signaling; and a further embodiment provides a method for the differentiation of liver bud progenitors into hepatic progenitors by one or more inhibitors of TGFβ signalling and/or fibroblast growth factor (FGF) inhibitors and/or one or more Notch inhibitors. Another embodiment discloses the differentiation of hepatic progenitors into hepatocyte-like cells or perivenous hepatocyte-like cells by one or more of Notch inhibitors and/or activators of glucocorticoid signalling and/or one or more activators of insulin signalling and/or one or more of ascorbic acid signalling activators and/or additional factors. Methods and kits for maintaining LB in self renewal state, hepatocyte-like cells in perivenous or periportal state, as well as surface markers for LB and mid/hindgut (MHG) cells are also disclosed.

公开(公告)号：US20150329821A1

公开(公告)日：2015-11-19

申请号：US14437147

申请日：2013-10-21

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Lay Teng ANG ,  Kyle M. LOH ,  Bing LIM

IPC: C12N5/0735 ,  C12N5/074

CPC classification number: C12N5/0606 ,  C12N5/0603 ,  C12N5/0672 ,  C12N5/0678 ,  C12N5/0696 ,  C12N2501/115 ,  C12N2501/15 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/385 ,  C12N2501/41 ,  C12N2501/415 ,  C12N2501/727 ,  C12N2501/998 ,  C12N2501/999 ,  C12N2506/02 ,  C12N2506/45 ,  C12N2533/52 ,  C12N2533/90

Abstract: The present disclosure provides an understanding of the regulation of the developmental phases of stem cells and their induction into relevant cell lineages, such as primitive streak, endoderm, mesoderm, or subterrotories of endoderm's. In particular, the present disclosure provides methods, culture medium and kits for the maintenance and differentiation of stem cells into relevant cell lineages.

Abstract translation: 本公开提供了对干细胞的发育阶段的调节及其对相关细胞谱系的诱导的理解，所述相关细胞系如内胚层的原始条纹，内胚层，中胚层或亚维管。 特别地，本公开提供了用于维持和分化干细胞到相关细胞谱系中的方法，培养基和试剂盒。

公开(公告)号：US20190309302A1

公开(公告)日：2019-10-10

申请号：US16345487

申请日：2017-10-16

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Uttam SURANA ,  Keng Boon WEE ,  Jing LIN ,  Bing LIM

IPC: C12N15/113 ,  A61P35/00 ,  A61K45/06 ,  A61K31/7088 ,  A61K9/00 ,  C12Q1/6886

Abstract: The present invention relates to antisense oligonucleotides for modulating the activity of glycine decarboxylase (GLDC). In particular, the present invention relates to antisense oligonucleotides capable of inducing exon skipping of RNA. Also claimed are pharmaceutical compositions, kits and methods of treating cancer and inducing exon-skipping using said antisense oligonucleotides. In addition, a method for aiding the categorising or determining prognosis of a cancer or in selecting a therapeutic strategy for a patient with cancer, based on assessing the level of GLDC nucleic acid, protein or activity in a sample derived from the patient is provided.

公开(公告)号：US20180072988A1

公开(公告)日：2018-03-15

申请号：US15565662

申请日：2016-04-11

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Xuyang SUN ,  Bing LIM

IPC: C12N5/0793 ,  G01N33/50 ,  G01N33/569 ,  C12N15/85

CPC classification number: C12N5/0619 ,  C12N15/85 ,  C12N2501/60 ,  C12N2501/65 ,  C12N2502/086 ,  C12N2506/02 ,  G01N33/5073 ,  G01N33/56966 ,  G01N2800/28

Abstract: The present disclosure provides a method of directly converting a stem cell into a lineage specific cell, comprising the steps of a) transfecting a stem cell with at least one expression vector comprising i) one or more cell lineage reprogramming factors operably linked to an inducible promoter and ii) a selection marker; and b) inducing the transfected stem cell from stem a) with an inducing agent to directly convert said stem cell into a lineage-specific cell. Particularly exemplified are methods of transfecting a stem cell with SA-ASCL1 (phospho-mutant), DLX2, LHX6 and miR-9/9*-124 linked to a doxycycline inducible promoter to convert the stem cell into an inhibitory neuron and transfecting with NeuroD2 linked to a doxycycline inducible promoter to convert a stem cell into an excitatory neuron. Methods of screening one or more factors and/or one or more genetic mutations that modulate a pre-selected activity of the lineage specific cell, kits and directly convertible stem cells obtained using method of the invention are also provided.

公开(公告)号：US20200325539A1

公开(公告)日：2020-10-15

申请号：US16092424

申请日：2017-04-06

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Bing LIM ,  Wencai ZHANG ,  Wai Leong TAM

IPC: C12Q1/6886 ,  C12N15/113 ,  A61K9/00

Abstract: The present disclosure relates to a method of determining the presence of lung cancer in a subject comprising the steps of detecting an expression level of miR-1246 alone or in combination with an expression level of miR-1290 in a sample obtained from the subject wherein the increase in miR-1246 and/or miR-1290 in the sample obtained from the subject relative to the expression level of miR-1246 or miR-1290 in the control sample indicates the presence of lung cancer in the subject. The disclosure further comprises a method of monitoring a response to therapy in a lung cancer patient, a method of prognosis of lung cancer in a patient and a method for treating lung cancer in a subject comprising the use of inhibitors of miR-1246 and/or miR-1290 alone or in combination. In a specific embodiment, miR-1246 and/or miR-1290 levels are used to predict response to chemotherapy and progression in human non-small cell lung cancer (NSCLC) patients.

公开(公告)号：US20190322987A1

公开(公告)日：2019-10-24

申请号：US16315624

申请日：2017-07-04

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Tong Ming LIU ,  Bing LIM ,  Pin LI

IPC: C12N5/0775 ,  C12N5/074 ,  A61K35/28

Abstract: The present disclosure provides a method of generating mature mesenchymal stem cells (MSC) from lateral plate mesoderm comprising culturing the lateral plate mesoderm cells on an extracellular matrix in a MSC cell culture media comprising (i) fibroblast growth factor; (ii) platelet-derived growth factor (PDGF); (iii) epidermal growth factor (EGF) and (iv) ascorbic acid. Also claimed are MSCs obtained by said culture method and a method of treating cartilage and bone disease in a patient using said cells. In addition, a culture medium for deriving primitive streak mesendoderm cells from pluripotent stem cells comprising (a) activin; (b) WNT-signalling activator; and/or (c) fibroblast growth factor and a culture medium for deriving lateral plate mesoderm cells from primitive streak mesendoderm cells comprising (1) fibroblast growth factor; (2) bone morphogenetic protein; (3) follistatin; and optionally Rho-associated protein kinase (ROCK) inhibitor are claimed.