研究者総覧

Suvd BYAMBAA (スブド ビャンバー)

  • 再生医学研究部 助教
メールアドレス: souvdjichi.ac.jp
Last Updated :2021/09/22

研究者情報

ホームページURL

ORCID ID

J-Global ID

研究キーワード

  • 再生医学   遺伝子治療   ゲノム編集   

研究分野

  • ライフサイエンス / 分子生物学

経歴

  • 2020年04月  自治医科大学 分子病態治療研究センター 再生医学研究部
  • 2018年04月 - 2020年03月  自治医科大学 分子病態治療研究センター 再生医学研究部

学歴

  • 2014年04月 - 2018年04月   自治医科大学   再生医学研究部

研究活動情報

論文

  • Suvd Byambaa, Hideki Uosaki, Tsukasa Ohmori, Hiromasa Hara, Hitoshi Endo, Osamu Nureki, Yutaka Hanazono
    Molecular therapy. Methods & clinical development 20 451 - 462 2021年03月 
    We conducted two lines of genome-editing experiments of mouse hematopoietic stem cells (HSCs) with the clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein 9 (Cas9). First, to evaluate the genome-editing efficiency in mouse bona fide HSCs, we knocked out integrin alpha 2b (Itga2b) with Cas9 ribonucleoprotein (Cas9/RNP) and performed serial transplantation in mice. The knockout efficiency was estimated at approximately 15%. Second, giving an example of X-linked severe combined immunodeficiency (X-SCID) as a target genetic disease, we showed a proof-of-concept of universal gene correction, allowing rescue of most of X-SCID mutations, in a completely non-viral setting. We inserted partial cDNA of interleukin-2 receptor gamma chain (Il2rg) into intron 1 of Il2rg via non-homologous end-joining (NHEJ) with Cas9/RNP and a homology-independent targeted integration (HITI)-based construct. Repaired HSCs reconstituted T lymphocytes and thymuses in SCID mice. Our results show that a non-viral genome-editing of HSCs with CRISPR/Cas9 will help cure genetic diseases.
  • Suvd Byambaa, Hideki Uosaki, Hiromasa Hara, Yasumitsu Nagao, Tomoyuki Abe, Hiroaki Shibata, Osamu Nureki, Tsukasa Ohmori, Yutaka Hanazono
    Experimental animals 69 2 189 - 198 2020年04月 [査読有り][通常論文]
     
    X-linked severe combined immunodeficiency (X-SCID) is an inherited genetic disorder. A majority of X-SCID subjects carries point mutations in the Interleukin-2 receptor gamma chain (IL2RG) gene. In contrast, Il2rg-knockout mice recapitulating X-SCID phenotype lack a large part of Il2rg instead of point mutations. In this study, we generated novel X-SCID mouse strains with small insertion and deletion (InDel) mutations in Il2rg by using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. To this end, we injected Streptococcus pyogenes Cas9 (SpCas9) mRNA and single guide RNA targeting the exon 2, 3 or 4 of Il2rg into mouse zygotes. In the F0 generation, we obtained 35 pups and 25 out of them were positive for Surveyor assay, and most of mutants displayed dramatic reductions of T and B lymphocytes in the peripheral blood. By amplicon sequencing, 15 out of 31 founder mice were determined as monoallelic mutants with possible minor mosaicisms while 10 mice were mosaic. Finally, we established new strains with 7-nucleotide deletion and 1-nucleotide insertions in the exon 2 and the exons 3 and 4, respectively. Although no IL2RG protein was detected on T cells of exons 3 and 4 mutants, IL2RG protein was unexpectedly detected in the exon 2 mutants. These data indicated that CRISPR/Cas9 targeting Il2rg causes InDel mutations effectively and generates genetically X-SCID mice. Genetic mutations, however, did not necessarily grant phenotypical alteration, which requires an intensive analysis after establishing a strain to confirm their phenotypes.

講演・口頭発表等

  • Phenotypical Correction of X-SCID Mice After CRISPR/Cas9-mediated UNIVERSAL Genome-Editing Therapy of Hematopoietic Stem Cells
    Suvd Byambaa, Hideki Uosaki, Hiromasa Hara, Hiroaki Shibata, Tomoyuki Abe, Yasumitsu Nagao, Osamu Nureki, Tsukasa Ohmori, Yutaka Hanazono
    Frontiers in Genome Engineering 2019年11月
  • Phenotypical Correction of X-SCID Mice After CRISPR/Cas9-mediated Genome-Editing Therapy of Hematopoietic Stem Cells
    Suvd Byambaa, Hideki Uosaki, Hiromasa Hara, Hiroaki Shibata, Tomoyuki Abe, Yasumitsu Nagao, Osamu Nureki, Tsukasa Ohmori, Yutaka Hanazono
    JSGCT 2019年07月
  • Genome Editing of Murine Hematopoietic Stem Cells by Cas9/RNP Targeting Integrin-alpha IIb Gene
    Suvd BYAMBAA, Hideki UOSAKI, Tsukasa OHMORI, Yutaka HANAZONO
    JSGE 2019年06月
  • Cure of X-SCID Mice After Ex Vivo Non-viral Genome-Editing Therapy of Hematopoietic Stem Cells
    Suvd Byambaa, Hideki Uosaki, Hiromasa Hara, Hiroaki Shibata, Tomoyuki Abe, Hiroko Hayakawa, Yasumitsu Nagao, Osamu Nureki, Tsukasa Ohmori, Yutaka Hanazono
    ASGCT 2019年05月
  • Targeted Gene Integration in Hematopoietic Stem and Progenitor Cells with Cas9-RNP Method to Universally Correct X-SCID Mutations
    Byambaa S, Uosaki H, Hara H, Shibata H, Abe T, Nagao Y, Nureki O, Ohmori T, Hanazono Y
    第41回日本分子生物学会年会 2018年11月30日 2018年11月
  • Targeted Genome Editing of Murine Hematopoietic Stem Cells by CRISPR/Cas9
    BYAMBAA S, UOSAKI H, HARA H, SHIBATA H, ABE T, NAGAO Y, NUREKI O, OHMORI T, HANAZONO Y
    日本遺伝子細胞治療学会学術集会 2018年07月
  • Novel SCID mice generation by CRISPR/Cas9
    BYAMBAA S, UOSAKI H, HARA H, SHIBATA H, ABE T, NAGAO Y, NUREKI O, OHMORI T, HANAZONO Y
    第65回日本実験動物学会 2018年05月
  • CRISPR/Cas9-Mediated Targeted Genome Editing of Hematopoietic Stem and Progenitor Cells
    Suvd BYAMBAA, Hideki UOSAKI, Hiromasa HARA, Hiroaki SHIBATA, Tomoyuki ABE, Yasumitsu NAGAO, Osamu NUREKI, Tsukasa OHMORI, Yutaka HANAZONO
    Takeda Symposium 2018年02月
  • Resistance of Mouse Hematopoietic Stem and Progenitor Cells to the Genome-Editing with Cas9
    Byambaa S, Uosaki H, Hara H, Abe T, Nagao Y, Nureki O, Ohmori T, Hanazono Y
    ASGCT 2017年05月

受賞

  • 2019年11月 Frontiers in Genome Engineering Young Scientist Award
  • 2019年05月 ASGCT Meritorious Abstract Travel Awards


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