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刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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基因治疗产品的质量控制分析方法及研究进展

Research progress in quality control analysis methods for gene therapy products

分类号:R917
出版年·卷·期(页码):2020,40 (1):4-12
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

基因治疗产品近年来已成为国内外药物研发的热点。对研发阶段的基因治疗产品开展质量研究,建立相应的质量控制方法和质量标准,是产品安全、有效的重要保证和产业化进程中的重要环节之一。基因治疗产品的质量控制项目包括鉴别、含量、效价、纯度、杂质和其他常规检测项目等。本文较为详细地介绍了在各种基因治疗产品中这些质控项目可采用的分析方法。对于新型基因治疗产品,迫切需要研究适当的分析方法进行有效的质量控制,而已批准上市或进入临床研究产品的质控方法和标准则需要进一步的提高和完善。

-----英文摘要:---------------------------------------------------------------------------------------

In recent years, gene therapy products have become a hot spot in drug R&D at home and abroad. For the gene therapy products in R&D stage, quality research should be conducted to establish corresponding quality control methods and standards, which is an important guarantee for product safety and effectiveness and one of the important steps in the industrialization process. Quality control items of gene therapy products include identification,content,potency,purity, impurities and other routine test items,etc. This paper describes in detail the analytical methods that can be used for these quality control items in various gene therapy products. For novel gene therapy products, it is urgent to develop appropriate analytical methods for effective quality control, while the quality control methods and standards for products which have already been approved for market or clinical research need to be further improved and perfected.

-----参考文献:---------------------------------------------------------------------------------------

[1] NALDINI L.Gene therapy returns to centre stage[J].Nature,2015,526(7573):351
[2] COLLINS M,THRASHER A.Gene therapy:progress and predictions[J].Proc Biol Sci,2015,282(1821):20143003
[3] KUMAR SR,MARKUSIC DM,BISWAS M,et al.Clinical development of gene therapy:results and lessons from recent successes[J].Mol Ther Methods Clin Dev,2016,3:16034
[4] LUKASHEV AN,ZAMYATNIN AA Jr.Viral vectors for gene therapy:current state and clinical perspectives[J].Biochemistry(Mosc),2016,81(7):700
[5] HOY SM.Onasemnogene abeparvovec:first global approval[J].Drugs,2019,79(4):1255
[6] 李永红,毕华,史新昌,等.人用基因治疗制品生产和质量控制的通用性技术要求[J].中国新药杂志,2018,27(21):2482 LI YH,BI H,SHI XC,et al.General technical requirements for production and quality control of human gene therapy products[J].Chin J New Drug,2018,27(21):2482
[7] 王军志生物技术药物研究开发和质量控制[M]第3版.北京:科学出版社,2018:876 WANG JZ.Research,Development and Quality Control of Biopharmaceuticals[M].3rd Ed.Beijing:Science Press,2018:876
[8] MITTEREDER N,MARCH KL,TRAPNELL BC.Evaluation of the concentration and bioactivity of adenovirus vectors for gene therapy[J].J Virol,1996,70(11):7498
[9] WHITFIELD RJ,BATTOM SE,BARUT M,et al.Rapid high-performance liquid chromatographic analysis of adenovirus type 5 particles with a prototype anion-exchange analytical monolith column[J].J Chromatogr A,2009,1216(13):2725
[10] GRIMM D,KERN A,PAWLITA M,et al.Titration of AAV-2 particles via a novel capsid ELISA:packaging of genomes can limit production of recombinant AAV-2[J].Gene Ther,1999,6(7):1322
[11] LOGAN AC,NIGHTINGALE SJ,HAAS DL,et al.Factors influencing the titer and infectivity of lentiviral vectors[J].Hum Gene Ther,2004,15(10):976
[12] ROSSI CA,KEARNEY BJ,OLSCHNER SP,et al.Evaluation of ViroCyt? Virus Counter for rapid filovirus quantitation[J].Viruses,2015,7(3):857
[13] KRAMBERGER P,CIRINGER M,?TRANCAR A,et al.Evaluation of nanoparticle tracking analysis for total virus particle determination[J].Virol J,2012,9:265
[14] WEATHERALL E,WILLMOTT GR.Applications of tunable resistive pulse sensing[J].Analyst,2015,140(10):3318
[15] BOUSSE T,SHORE DA,GOLDSMITH CS,et al.Quantitation of influenza virus using field flow fractionation and multi-angle light scattering for quantifying influenza A particles[J].J Virol Methods,2013,193(2):589
[16] MA L,BLUYSSEN HA,DE RAEYMAEKER M,et al.Rapid determination of adenoviral vector titers by quantitative real-time PCR[J].J Virol Methods,2001,93(1-2):181
[17] WERLING NJ,SATKUNANATHAN S,THORPE R,et al.Systematic comparison and validation of quantitative real-time PCR methods for the quantitation of adeno-associated viral products[J].Hum Gene Ther Methods,2015,26(3):82
[18] GRIEGER JC,CHOI VW,SAMULSKI RJ.Production and characterization of adeno-associated viral vectors[J].Nat Protoc,2006,1(3):1412
[19] SANMIGUEL J,GAO G,VANDENBERGHE LH.Quantitative and digital droplet-based AAV genome titration[J].Methods Mol Biol,2019,1950:51
[20] LABARRE DD,LOWY RJ.Improvements in methods for calculating virus titer estimates from TCID50 and plaque assays[J].J Virol Methods,2001,96(2):107
[21] MURAKAMI P,HAVENGA M,FAWAZ F,et al.Common structure of rare replication-deficient E1-positive particles in adenoviral vector batches[J].J Virol,2004,78(12):6200
[22] WANG F,PUDDY AC,MATHIS BC,et al.Using QPCR to assign infectious potencies to adenovirus based vaccines and vectors for gene therapy:toward a universal method for the facile quantitation of virus and vector potency[J].Vaccine,2005,23(36):4500
[23] AZIZI A,TANG M,GISONNI-LEX L,et al.Evaluation of infectious titer in a candidate HSV type 2 vaccine by a quantitative molecular approach[J].BMC Microbiol,2013,13:284
[24] ZEN Z,ESPINOZA Y,BLEU T,et al.Infectious titer assay for adeno-associated virus vectors with sensitivity sufficient to detect single infectious events[J].Hum Gene Ther,2004,15(7):709
[25] SALVETTI A,ORèVE S,CHADEUF G,et al.Factors influencing recombinant adeno-associated virus production[J].Hum Gene Ther,1998,9(5):695
[26] BARDE I,SALMON P,TRONO D.Production and titration of lentiviral vectors[J].Curr Protoc Neurosci,2010,53(1):4.21.1
[27] 刁勇,王启钊,吕颖慧,等.重组腺相关病毒基因药物的病毒滴度定量测定[J].中国新药与临床杂志,2010,29(10):728 DIAO Y,WANG QZ Lü YH,et al.Biological assay of recombinant adeno-associated virus gene medicine[J].Chin J New Drugs Clin Rem,2010,29(10):728
[28] PALMER DJ,NG P.Physical and infectious titers of helper-dependent adenoviral vectors:a method of direct comparison to the adenovirus reference material[J].Mol Ther,2004,10(4):792
[29] D'COSTA S,BLOUIN V,BROUCQUE F,et al.Practical utilization of recombinant AAV vector reference standards:focus on vector genomes titration by free ITR qPCR[J].Mol Ther Methods Clin Dev,2016,5:16019
[30] BLOTTA I,PRESTINACI F,MIRANTE S,et al.Quantitative assay of total dsDNA with PicoGreen reagent and real-time fluorescent detection[J].Ann Ist Super Sanita,2005,41(1):119
[31] ZHOU Y,MAO S,LI Y,et al.Improved fluorometric DNA determination based on the interaction of the DNA/polycation complex with Hoechst 33258[J].Microchim Acta,2004, 144(1-3):191
[32] MOTAé,SOUSA ?,?ERNIGOJ U,et al.Rapid quantification of supercoiled plasmid deoxyribonucleic acid using a monolithic ion exchanger[J].J Chromatogr A,2013,1291:114
[33] FAWAZ FS,ELSHEIKH MA,OGAWA Y,et al.A potency assay for a replication incompetent adenovirus type 5 carrying a human fgf-4 gene[J].Anal Biochem,2005,342(1):34
[34] ROMAN AJ,BOYE SL,ALEMAN TS,et al.Electroretinographic analyses of Rpe65-mutant rd12 mice:developing an in vivo bioassay for human gene therapy trials of Leber congenital amaurosis[J].Mol Vis,2007,13:1701
[35] WAERNER T,GIRSCH T,VARGA S,et al.A receptor-binding-based bioassay to determine the potency of a plasmid biopharmaceutical encoding VEGF-C[J].Anal Bioanal Chem,2007,389(7-8):2109
[36] HUANG L,CHIN E,CHIANG YL.Development of potency assays for a plasmid containing vascular endothelial growth factor 2[J].Electron J Biotechnol,2010,13(1):1
[37] YAMAGUCHI T,UCHIDA E.Oncolytic virus:regulatory aspects from quality control to clinical studies[J].Curr Cancer Drug Targets,2018,18(2):202
[38] WANG X,MORGAN DM,WANG G,et al.Residual DNA analysis in biologics development:review of measurement and quantitation technologies and future directions[J].Biotechnol Bioeng,2012,109(2):307
[39] WRIGHT JF.Manufacturing and characterizing AAV-based vectors for use in clinical studies[J].Gene Ther,2008,15(11):840
[40] THORNE BA,QUIGLEY P,NICHOLS G,et al.Characterizing clearance of helper adenovirus by a clinical rAAV1 manufacturing process[J].Biologicals,2008,36(1):7
[41] YE GJ,SCOTTI MM,LIU J,et al.Clearance and characterization of residual HSV DNA in recombinant adeno-associated virus produced by an HSV complementation system[J].Gene Ther,2011,18(2):135
[42] ALLAY JA,SLEEP S,LONG S,et al.Good manufacturing practice production of self-complementary serotype 8 adeno-associated viral vector for a hemophilia B clinical trial[J].Hum Gene Ther,2011,22(5):595
[43] WRIGHT JF.Product-related impurities in clinical-grade recombinant AAV vectors:characterization and risk assessment[J].Biomedicines,2014,2(1):80
[44] SCHN?DT M,BüNING H.Improving the quality of adeno-associated viral vector preparations:the challenge of product-related impurities[J].Hum Gene Ther Methods,2017,28(3):101
[45] RODRIGUES GA,SHALAEV E,KARAMI TK,et al.Pharmaceutical development of AAV-based gene therapy products for the eye[J].Pharm Res,2018,36(29):1
[46] ALLAY JA,SLEEP S,LONG S,et al.Good manufacturing practice production of self-complementary serotype 8 adeno-associated viral vector for a hemophilia B clinical trial[J].Hum Gene Ther,2011,22(5):595
[47] TAKAHASHI E,COHEN SL,TSAI PK,et al.Quantitation of adenovirus type 5 empty capsids[J].Anal Biochem,2006,349(2):208
[48] BURNHAM B,NASS S,KONG E,et al.Analytical ultracentrifugation as an approach to characterize recombinant adeno-associated viral vectors[J].Hum Gene Ther Methods,2015,26(6):228
[49] YANG X,AGARWALA S,RAVINDRAN S,et al.Determination of particle heterogeneity and stability of recombinant adenovirus by analytical ultracentrifugation in CsCl gradients[J].J Pharm Sci,2008,97(2):746
[50] PIERSON EE,KEIFER DZ,ASOKAN A,et al.Resolving adeno-associated viral particle diversity with charge detection mass spectrometry[J].Anal Chem,2016,88(13):6718
[51] KONZ JO,LEE AL,LEWIS JA,et al.Development of a purification process for adenovirus:controlling virus aggregation to improve the clearance of host cell DNA[J].Biotechnol Prog,2005,21(2):466
[52] WRIGHT JF,LE T,PRADO J,et al.Identification of factors that contribute to recombinant AAV2 particle aggregation and methods to prevent its occurrence during vector purification and formulation[J].Mol Ther,2005,12(1):171
[53] KAHLER AM,CROMEANS TL,METCALFE MG,et al.Aggregation of adenovirus 2 in source water and impacts on disinfection by chlorine[J].Food Environ Virol,2016,8(2):148
[54] MCEVOY M,RAZINKOV V,WEI Z,et al.Improved particle counting and size distribution determination of aggregated virus populations by asymmetric flow field-flow fractionation and multiangle light scattering techniques[J].Biotechnol Prog,2011,27(2):547
[55] SHIH SJ,YAGAMI M,TSENG WJ,et al.Validation of a quantitative method for detection of adenovirus aggregation[J].Bioprocess J,2011,9(2):25
[56] KRAMBERGER P,CIRINGER M,?TRANCAR A,et al.Evaluation of nanoparticle tracking analysis for total virus particle determination[J].Virol J,2012,265:1
[57] SMITH CR,DEPRINCE RB,DACKOR J,et al.Separation of topological forms of plasmid DNA by anion-exchange HPLC:shifts in elution order of linear DNA[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,854(1-2):121
[58] SCHMIDT T,FRIEHS K,SCHLEEF M,et al.Quantitative analysis of plasmid forms by agarose and capillary gel electrophoresis[J].Anal Biochem,1999,274(2):235
[59] CHUAH MK,COLLEN D,VANDENDRIESSCHE T.Biosafety of adenoviral vectors[J].Curr Gene Ther,2003,3(6):527
[60] SCHALK JA,DE VRIES CG,ORZECHOWSKI TJ,et al.A rapid and sensitive assay for detection of replication-competent adenoviruses by a combination of microcarrier cell culture and quantitative PCR[J].J Virol Methods,2007,145(2):89
[61] FALLAUX FJ,BOUT A,van der VELDE I,et al.New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses[J].Hum Gene Ther,1998,9(13):1909
[62] MARZIO G,KERKVLIET E,BOGAARDS JA,et al.A replication-competent adenovirus assay for E1-deleted Ad35 vectors produced in PER.C6 cells[J].Vaccine,2007,25(12):2228
[63] ZHANG WW,KOCH PE,ROTH JA.Detection of wild-type contamination in a recombinant adenoviral preparation by PCR[J].Biotechniques,1995,18(3):444
[64] PUNTEL M,CURTIN JF,ZIRGER JM,et al.Quantification of high-capacity helper-dependent adenoviral vector genomes in vitro and in vivo,using quantitative TaqMan real-time polymerase chain reaction[J].Hum Gene Ther,2006,17(5):531
[65] SCHALK JA,de VRIES CG,ORZECHOWSKI TJ,et al.A rapid and sensitive assay for detection of replication-competent adenoviruses by a combination of microcarrier cell culture and quantitative PCR[J].J Virol Methods,2007,145(2):89
[66] LI F,FENG L,LIU Y,et al.An integrated cell culture and quantitative polymerase chain reaction technique for determining titers of functional and infectious adenoviruses[J].Anal Biochem,2009,391(2):157
[67] CHONG H,STARKEY W,VILE RG.A replication-competent retrovirus arising from a split-function packaging cell line was generated by recombination events between the vector,one of the packaging constructs,and endogenous retroviral sequences[J].J Virol,1998,72(4):2663
[68] DONAHUE RE,KESSLER SW,BODINE D,et al.Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer[J].J Exp Med,1992,176(4):1125
[69] LONG Z,LI LP,GROOMS T,et al.Biosafety monitoring of patients receiving intracerebral injections of murine retroviral vector producer cells[J].Hum Gene Ther,1998,9(8):1165
[70] MARTINEAU D,KLUMP WM,MCCORMACK JE,et al.Evaluation of PCR and ELISA assays for screening clinical trial subjects for replication-competent retrovirus[J].Hum Gene Ther,1997,8(10):1231
[71] HASHIMOTO-GOTOH A,YOSHIKAWA R,MIYAZAWA T.Comparison between S+L-assay and LacZ marker rescue assay for detecting replication-competent gammaretroviruses[J].Biologicals,2015,43(5):363
[72] ROTHE M,MODLICH U,SCHAMBACH A.Biosafety challenges for use of lentiviral vectors in gene therapy[J].Curr Gene Ther,2013,13(6):453
[73] CORNETTA K,YAO J,JASTI A,et al.Replication-competent lentivirus analysis of clinical grade vector products[J].Mol Ther,2011,19(3):557
[74] SKRDLANT LM,ARMSTRONG RJ,KEIDAISCH BM,et al.Detection of replication competent lentivirus using a qPCR assay for VSV-G[J].Mol Ther Methods Clin Dev,2018,8:1
[75] SASTRY L,XU Y,DUFFY L,et al.Product-enhanced reverse transcriptase assay for replication-competent retrovirus and lentivirus detection[J].Hum Gene Ther,2005,16(10):1227
[76] MARCUCCI KT,JADLOWSKY JK,HWANG WT,et al.Retroviral and lentiviral safety analysis of gene-modified T cell products and infused HIV and oncology patients[J].Mol Ther,2018,26(1):269
[77] WORKING PK,LIN A,BORELLINI F.Meeting product development challenges in manufacturing clinical grade oncolytic adenoviruses[J].Oncogene,2005,24(52):7792
[78] SHIH SJ,MIYASHITA-LIN E,TSENG WJ,et al.Use of a bioamplification assay to detect nonselective recombinants and assess the genetic stability of oncolytic adenoviruses[J].Hum Gene Ther,2010,21(12):1707

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