Method of producing induced pluripotent stem cells using inhibitors of P53
    35.
    发明授权
    Method of producing induced pluripotent stem cells using inhibitors of P53 有权
    使用P53抑制剂产生诱导多能干细胞的方法

    公开(公告)号:US09404124B2

    公开(公告)日:2016-08-02

    申请号:US14533080

    申请日:2014-11-04

    申请人: Kyoto University

    IPC分类号: C12N5/00 C12N15/85 C12N5/074

    摘要: Provided is a method of producing an iPS cell, comprising bringing (a) Oct3/4 or a nucleic acid that encodes the same, (b) Klf4 or a nucleic acid that encodes the same, and (c) Sox2 or a nucleic acid that encodes the same, as well as (d1) L-Myc or a nucleic acid that encodes the same and/or (d2) a functional inhibitor of p53, into contact with a somatic cell. It is preferable that (a) a nucleic acid that encodes Oct3/4, (b) a nucleic acid that encodes Klf4, (c) a nucleic acid that encodes Sox2, (d1) a nucleic acid that encodes L-Myc and (e) a nucleic acid that encodes Lin28 or Lin28b be inserted into an episomal vector having loxP sequences placed in the same orientation on the 5′ and 3′ sides of a vector constituent essential for the replication of the vector, that (d2) a nucleic acid that encodes an shRNA against p53 be inserted into a vector ensuring transient expression (plasmid vector and the like), and that all these nucleic acids be transferred to a somatic cell.

    摘要翻译: 本发明提供一种iPS细胞的制造方法,其特征在于:(a)Oct3 / 4或其编码的核酸,(b)Klf4或其编码的核酸,以及(c)Sox2或所述核酸, 编码相同的,以及(d1)L-Myc或编码与p53的功能性抑制剂相同和/或(d2)的核酸与体细胞接触。 优选(a)编码Oct3 / 4的核酸,(b)编码Klf4的核酸,(c)编码Sox2的核酸,(d1)编码L-Myc的核酸和(e )将编码Lin28或Lin28b的核酸插入具有放置在与载体复制必需的载体成分的5'和3'侧相同取向上的loxP序列的附加型载体中,(d2)核酸 将编码针对p53的shRNA插入到确保瞬时表达(质粒载体等)的载体中,并将​​所有这些核酸转移到体细胞。

    COMPOSITION FOR MAINTAINING CHROMOSOMAL STABILITY OF PLURIPOTENT STEM CELLS, CONTAINING SMALL-MOLECULE COMPOUND
    38.
    发明申请
    COMPOSITION FOR MAINTAINING CHROMOSOMAL STABILITY OF PLURIPOTENT STEM CELLS, CONTAINING SMALL-MOLECULE COMPOUND 有权
    用于维持含有小分子化合物的细胞干细胞的染色体稳定性的组合物

    公开(公告)号:US20160160183A1

    公开(公告)日:2016-06-09

    申请号:US14906547

    申请日:2014-07-22

    IPC分类号: C12N5/074

    摘要: The present invention relates to a composition for maintaining the chromosomal stability of pluripotent stem cells, which contains a small-molecule compound, and more particularly, to a composition for maintaining the chromosomal stability of induced pluripotent stem cells, which contains a ROCK inhibitor, a MEK inhibitor, an ALK5 inhibitor or an antioxidant, which is capable of inhibiting chromosomal structural and numerical mutations or DNA damage during induction of induced pluripotent stem cell and the subsequent culture of the cells. The small-molecule compound-containing composition for maintaining the chromosomal stability of induced pluripotent stem cells increases the reprogramming rate and efficiency during production of induced pluripotent stem cells and exhibits excellent effects on the inhibition of chromosomal structural and numerical mutations or DNA damage. Thus, the composition of the present invention is very useful for the development of induced pluripotent stem cell therapeutic agents having excellent chromosomal stability.

    摘要翻译: 本发明涉及用于维持含有小分子化合物的多能干细胞的染色体稳定性的组合物,更具体地,涉及用于维持诱导多能干细胞的染色体稳定性的组合物,其含有ROCK抑制剂, MEK抑制剂,ALK5抑制剂或抗氧化剂,其能够在诱导的多能干细胞诱导期间抑制染色体结构和数值突变或DNA损伤,并随后培养细胞。 用于维持诱导多能干细胞染色体稳定性的小分子化合物组合物在诱导多能干细胞的产生过程中增加了重编程速率和效率,并且对抑制染色体结构和数值突变或DNA损伤表现出极好的效果。 因此,本发明的组合物对于具有优异的染色体稳定性的诱导多能干细胞治疗剂的开发非常有用。