| 研究課題/領域番号 |
23K15377
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分54030:感染症内科学関連
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| 研究機関 | 自治医科大学 |
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研究代表者 |
アデリーン ヨオシーンリアン 自治医科大学, 医学部, ポスト・ドクター (20956156)
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| 研究期間 (年度) |
2023-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2024年度: 2,600千円 (直接経費: 2,000千円、間接経費: 600千円)
2023年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
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| キーワード | CRISPR-Cas13 / engineered phage / synthetic platform / antimicrobial agent / engineered bacteriophage |
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| 研究開始時の研究の概要 |
MRSA infections need novel treatments. Developed antimicrobial capsid that kills target bacteria in a CRISPR-Cas13a sequence-specific manner has low yield and weak bactericidal effect. This study would result in high-yield engineered phage and enhanced bactericidal activity by synthetic method.
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| 研究実績の概要 |
The purpose of the research is to enhance bactericidal efficacy against MRSA by high-yield synthetic phage loaded with CRISPR-Cas13 that specifically targets drug resistance gene mecA. In this year I have successfully established the technology that reboots phages in the L-form cells of S. aureus. I have modified the phage genome to a smaller size to increase phage yield and bactericidal activity. I have constructed smaller genome-sized synthetic phages carrying CRISPR-Cas13a, CRISPR-Cas13b, CRISPR-Cas13x and CRISPR-Cas13y and compared the bactericidal activity against MRSA. I found CRISPR-Cas13a showed the strongest activity among all the CRISPR-Cas13 subtypes. I have also started on establishing the in vivo evaluation model in the MRSA infected neonatal mouse.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
As I have successfully achieved my objectives of 2023 research plan, I have started to establish an in vivo evaluation model for the synthetic phages in MRSA infected neonatal mouse. This experiment requires many optimization as the MRSA infection neonatal mouse model has not been reported before and the factors of phage titre and frequency of treatment needed to be taken into consideration.
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| 今後の研究の推進方策 |
Currently, the modified synthetic phage loaded with the CRISPR-Cas13a showed the strongest bactericidal activity across all the other subtypes. However, the bactericidal activity of the orthologues of the CRISPR-Cas13a is still unknown. I will compare the bactericidal efficacy of modified synthetic phages that are loaded with different CRISPR-Cas13a orthologues. I will then evaluate the efficacy of the phages in the established MRSA neonatal mouse. As a result from this plan, I hope to successfully develop a highly efficient CRISPR-Cas13-antimicrobials agent against MRSA that can be used in the clinical setting.
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