Leveraging rAAV bioprocess understanding and next generation bioanalytics development

被引：14

作者：

Escandell, Jose M. ^{[1
,2
]}

Pais, Daniel Am ^{[1
,2
]}

Carvalho, Sofia B. ^{[1
,2
]}

Vincent, Karen ^{[3
]}

Gomes-Alves, Patricia ^{[1
,2
]}

Alves, Paula M. ^{[1
,2
,4
,5
]}

机构：

[1] Inst Biol Expt & Tecnol, iBET, Apartado 12, P-2780901 Oeiras, Portugal

[2] Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, ITQB NOVA, Av Repebl, P-2780157 Oeiras, Portugal

[3] Sanofi, 49 New York Ave, Framingham, MA 01701 USA

[4] Inst Biol Expt & Tecnol, iBET, Anim Cell Technol Unit, Apartado 12, P-2781901 Oeiras, Portugal

[5] Inst Tecnol Quim & Biol, ITQB NOVA, Apartado 12, P-2781901 Oeiras, Portugal

来源：

CURRENT OPINION IN BIOTECHNOLOGY | 2022年 / 74卷

关键词：

GENE-THERAPY; VECTOR;

D O I：

10.1016/j.copbio.2021.12.009

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Recombinant adeno-associated (rAAV) vector-based gene therapy has been the focus of intense research driven by the safety profile and several recent clinical breakthroughs. As of April 2021, there are two rAAV-based gene therapies approved and more than two-hundred active clinical trials (approximately thirty in Phase III). However, the expected increase in demand for rAAV vectors still poses several challenges. Discussed herein are key aspects related to R&D needs and Chemistry, Manufacturing and Control (CMC) efforts required to attend this growing demand. Authors provide their perspective on strategic topics for rAAV-based therapies success: scalability and productivity; improved safety; increased process understanding combined with development of orthogonal bioanalytics that are able to identify, monitor and control Critical Quality Attributes (CQAs) during bioprocessing.

引用

页码：271 / 277

页数：7

共 56 条

[1] Affecting HEK293 Cell Growth and Production Performance by Modifying the Expression of Specific Genes [J].

Abaandou, Laura ;

Quan, David ;

Shiloach, Joseph .

CELLS, 2021, 10 (07)

[2] Moving from the bench towards a large scale, industrial platform process for adeno-associated viral vector purification [J].

Adams, Benjamin ;

Bak, Hanne ;

Tustian, Andrew D. .

BIOTECHNOLOGY AND BIOENGINEERING, 2020, 117 (10) :3199-3211

[3] Site-Specific N-Glycosylation on the AAV8 Capsid Protein [J].

Aloor, Arya ;

Zhang, Junping ;

Gashash, Ebtesam A. ;

Parameswaran, Aishwarya ;

Chrzanowski, Matthew ;

Ma, Cheng ;

Diao, Yong ;

Wang, Peng George ;

Xiao, Weidong .

VIRUSES-BASEL, 2018, 10 (11)

[4] High-dose AAV gene therapy deaths [J].

不详 .

NATURE BIOTECHNOLOGY, 2020, 38 (08) :910-910

[5] FDA approves hereditary blindness gene therapy [J].

不详 .

NATURE BIOTECHNOLOGY, 2018, 36 (01) :6-6

[6]

Ansorge S, 2019, CELL GENE THER INSIG, V5, P1719

[7] Analytical Ultracentrifugation as an Approach to Characterize Recombinant AAV Vectors [J].

Burnham, Brenda ;

Nass, Shelley ;

Kong, Elton ;

Mattingly, MaryEllen ;

Woodcock, Denise ;

Song, Tony ;

Cheng, Seng ;

Scaria, Abraham ;

O'Riordan, Catherine .

MOLECULAR THERAPY, 2015, 23 :S223-S223

[8]

Daley J, 2019, NATURE, V576, pS12

[9] Accurate Quantification and Characterization of Adeno-Associated Viral Vectors [J].

Dobnik, David ;

Kogovsek, Polona ;

Jakomin, Tjasa ;

Kosir, Nejc ;

Znidaric, Magda Tusek ;

Leskovec, Maja ;

Kaminsky, Stephen M. ;

Mostrom, Janet ;

Lee, Hyunmi ;

Ravnikar, Maja .

FRONTIERS IN MICROBIOLOGY, 2019, 10

[10] Two-Dimensional Droplet Digital PCR as a Tool for Titration and Integrity Evaluation of Recombinant Adeno-Associated Viral Vectors [J].

Furuta-Hanawa, Birei ;

Yamaguchi, Teruhide ;

Uchida, Eriko .

HUMAN GENE THERAPY METHODS, 2019, 30 (04) :127-136

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