| Project/Area Number |
18K16180
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Nakamura Tomofumi 熊本大学, 大学院生命科学研究部(医), 研究員 (00772526)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | HIV-1感染症 / 新規HIV-1治療法 / HIV-1ゲノム編集 / CRISPA-Cas9 / HIV-1 / AAV / SaCas9 / GesicleCRISPR/Cas9 / 潜伏感染 |
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| Outline of Final Research Achievements |
HIV-1 DNA elimination from the human body was required for HIV-1 cure as a next generation therapy. We created a novel modified CRISPR-Cas9 to cut the HIV proviral remaining in the infected cells and utilized adeno-associated virus (rAAV) or exosomes like parcels (Gesicle) as delivery systems, producing a new HIV-1 genome editing system in vitro. However, HIV-1 infectivity ability and replication fitness was so powerful that the only new systems did not inhibit the HIV-1 proliferation. Even though the addition of some HIV-1 drugs after HIV-1 infection, it was hard to eliminate HIV-1 provirus from the infected cells. Further improvement of these tools was required for HIV-1 provirus elimination from HIV-1 infected cells.
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| Academic Significance and Societal Importance of the Research Achievements |
HIV感染症は、combination antiviral therapy（cART）が唯一の治療法であるが、服薬を中止すると体内のHIVリザーバーからHIV が再増殖するため、生涯にわたりcARTを継続しなければならない。ゆえに『HIV治癒』に向けて斬新で画期的な新規治療法の開発が必要不可欠な状況である。問題となるHIVリザーバーの一因として、HIVのプロウイルス状態(感染細胞に増殖可能なHIV-1 DNAが残存）が指摘されているが、このHIVプロウイルスの排除法を開発することが『HIV治癒』に向けて必須のステップになると考えられる。
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