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[Data Link] rAAV vector/遺伝子治療薬に関する文献調査 [~2020/08/24] – ID2033 [2019/09/13]

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Key Considerations in Gene Therapy Manufacturing for Commercialization, 2018 – Cell Culture DISH
(1) Phase 1 Clinical Study: 18 month (breakthrough), Several months (Traditional BLA)
(2) Decision on BT Application: – (BT), N/A (TD)
(3) EOP 1 Meeting Confirms BT Therapy Study: 6 months (BT), N/A (TD)
(4) Phase 2/3 Clinical Study: 24 months (BT), P2:Several Mo. to 2y and P3:1 to 4y (TD)
(5) EOP 3/Pre-NDA/Pre-BLA Submission Meeting: -, –
(6) NDA/BLA Preparation: 6months(BT), – (TD)
(7) NDA/BLA Review: 6months(BT), 10months(TD)
(8) Development Timeline: ~5.2y (BT), ~7.4y(TD)
・Plasmid Manufacturing : Fermentation→Plasmid Recovery→Purification→Fromulatiion→(Transfect)
・Viral Manufacturing: Expand→(Transfect)→Clarification→Concentration→Purifiation→Sterilization→(Activate & Modify)
・Cell Processing: Isolate & Enrich→(Activate & Modify)→Expand→Harvest→Formulation

Viruses used: Retrovirus, Lentivirus, AAV and Adenovirus.
iCELLis Nano, 500の情報、Allegro single use bioreactor
DSP platform : 3 chromatography system.
Transfection System
Analytical Method
https://cellculturedish.com/wp-content/uploads/2018/09/Key-Considerations-Gen-Therapy-Manufacturing-Commercialization.pdf

Methods Matter — Standard Production Platforms For Recombinant AAV Can Produce Chemically And Functionally Distinct Vectors, 2019 –
https://www.biorxiv.org/content/10.1101/640169v2.full.pdf

Pharmacology of Recombinant Adeno-associated Virus Production, 2018 – mol Ther Methods Clin Dev. 2018 Mar 16; 8: 166-180 –
ベクターが大きいとFull率は低下する。トリプル-インフェクションでは、更にfull率は低下する。

rAAV2-FIX vectors in A549-derived producer cell line
(1) full particels : 8%~13%

rAAV2 vectors inHEK293 cells
(1) full particles : up to 74% for a 3.4kb-vector, 40%~45% for a 4.2kb-vector
(2) full particles: 8% and 10%~12% by triple-transfection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908265/

Manufacturing of viral vectors for gene therapy: part I. Upstream processing, 2014 – Pharmaceutical BIOPROCESSING –

https://www.openaccessjournals.com/articles/manufacturing-of-viral-vectors-for-gene-therapy-part-i-upstream-processing.pdf

Pharmacology of Recombinant Adeno-associated Virus Production, 2018
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908265/

In Vitro Packaging of Adeno-Associated Virus DNA ,1998
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC109794/

Pharmacology of Recombinant Adeno-associated Virus Production
Magalie Penaud-Budloo, Achille François, Nat, 2018

Next-generation AAV vectors—do not judge a virus (only) by its cover , 2019, AviGen GmbH source – ベクター開発、発現制御、プロモーター

CATAPULT, UKにおける遺伝子治療、Cell Therapy, Viral Vectors, 製造・分析、クリニカル、Webinar開催など、網羅的に関係する情報の宝庫 soruce

Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293 Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and FLT1 Clinical Vector, 2018

A scalable method for the production of high-titer and high-quality adeno-associated type 9 vectors using the HSV platform, 2016

Enhancement of Adeno-Associated Virus Infection by Mobilizing Capsids into and Out of the Nucleolus
, (2009) AAV2の感染時、核小体への導入効率の向上薬剤(MG132とHU)

Scalable Production of AAV Vectors in Orbitally Shaken HEK293 Cells (2019)

Quantification of Adeno-Associated Virus Particles and Empty Capsids by Optical Density Measurement (2003)

特許公報(B2)_アデノ随伴ウイルス（ＡＡＶ）血清型９の配列、それを含むベクターおよびその使用、配列が特許になっている。

特許公報(B2)_アデノ随伴ウイルス（ＡＡＶ）血清型８の配列

AAVベクターの製造・品質に関するリフレクションペーパー (pmda

https://www.pmda.go.jp/files/000221591.pdf

平成29年度我が国におけるデータ駆動型社会に係る基盤整備「根本治療の実現」に向けた適切な支援のあり方の調査

https://www.meti.go.jp/meti_lib/report/H29FY/000111.pdf

遺伝子組換え生物に係る
法規制の動向について
独立行政法人製品評価技術基盤機構バイオテクノロジーセンター (Biological Resource Center, NITE ; NBRC)

https://www.kansai.meti.go.jp/2-4bio/kansai_smartcell/180925_4.pdf

バイオ戦略の策定に向けた検討
バイオテクノロジーによるイノベーションを通じて実現を目指す経済社会像(ビジョン)

https://www8.cao.go.jp/cstp/tyousakai/bio/1kai/siryo4.pdf

遺伝子治療とゲノム編集治療の研究開発の現状と課題
Since 1874

https://www.kantei.go.jp/jp/singi/kenkouiryou/genome/advisory_board/dai4/siryou4-1.pdf

ウイルスを基盤とした遺伝子治療薬の臨床開発の
現状と今後の展望

https://www.jstage.jst.go.jp/article/dds/34/2/34_99/_pdf/-char/ja

ex vivo遺伝子治療用製品の品質管理戦略の留意点

Points to consider on quality control strategy for ex vivo gene therapy products

http://jsgt.jp/CLINICAL_STUDY/2018-1pmda.pdf

脳卒中に対する遺伝子治療の現状と将来

http://cbfm.mtpro.jp/journal2/contents/assets/016030167.pdf

AAV を利用した遺伝子治療
小澤敬也

http://jsv.umin.jp/journal/v57-1pdf/virus57-1_047-056.pdf

アデノ随伴ウイルス(AAV)ベクターによる遺伝子治療　(2003)

AAP (Assembly Activating Proteins)

A Quantitative Dot Blot Assay for AAV Titration and Its Use for Functional Assessment of the Adeno-associated Virus Assembly-activating Proteins

生物多様性影響評価書

科学研究費助成事業研究成果報告書

適正製造規範に適合する簡易精製が可能な次世代AAVベクターの開発

PMDA

厚生労働省精神・神経疾患研究委託費

遺伝性筋疾患に対する分子治療の基盤研究

病原体検出マニュアル　(国立感染実用研究所)

AAV education Vector

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