2020 Fiscal Year Final Research Report
Establishing of new AAV vector system against neutral antibody
| Project/Area Number |
19K16526
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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 48040:Medical biochemistry-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | AAVベクター / 修飾法 |
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| Outline of Final Research Achievements |
We aimed to develop a new adeno-associated virus (AAV) vector, which when surface modified, was able to escape the immune system in vivo. At first, we modified the viral protein 2 (VP2) in the AAV vector plasmid as done in previous studies (Warrington, KH., et al. J. Virol. 2004). Although we observed the tagged protein on the vector’s surface, both the vector’s dose and infectious ability decreased significantly in the presence of high doses of anti-AAV antibodies because of its limited surface modification. Therefore, by targeting the vector’s surface protein, we developed a newly modified AAV vector. This new vector expressed the ligands against the receptor, which is expressed in liver tissue. We found that the vector’s dose and infectious ability against the HEK293 cells were the same as those seen with the conventional AAV vector.
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| Free Research Field |
遺伝子治療
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| Academic Significance and Societal Importance of the Research Achievements |
AAVベクター自身にヒトに対して病原性がなく、宿主ゲノムに挿入されずエピゾーム中にて遺伝子を発現するため、安全な遺伝子治療用ベクターとして多くの臨床試験が行われている。しかし、増殖細胞では遺伝子発現が徐々に失われることや既感染に伴う抗AAV中和抗体存在下では感染性を消失することが問題となる。本研究によって開発したAAVベクター表面修飾法は、これまで困難であったAAVベクターの修飾を可能とし、血清型によらず標的臓器への感染性を上昇させるだけでなく、中和抗体存在下でも感染する可能性を示した。
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