A novel mixing device for the reproducible generation of nonviral gene therapy formulations

被引：12

作者：

Davies, Lee A. ^{[1
]}

Nunez-Alonso, Graciela A. ^{[1
]}

Hebel, Henry L. ^{[2
]}

Scheule, Ron K. ^{[3
]}

Cheng, Seng H. ^{[3
]}

Hyde, Stephen C. ^{[1
]}

Gill, Deborah R. ^{[1
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Gene Med Grp, Oxford OX3 9DU, England

[2] VGXI, Houston, TX USA

[3] Genzyme Corp, Framingham, MA 01701 USA

来源：

BIOTECHNIQUES | 2010年 / 49卷 / 03期

关键词：

Gene therapy; nonviral formulations; lipoplexes; polyplexes; DNA COMPLEXES; PLASMID DNA; EXPRESSION; SHEAR; LUNG;

D O I：

10.2144/000113498

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Nonviral gene therapy utilizing plasmid DNA (pDNA) complexed with cationic lipids (lipoplexes) or cationic polymers (polyplexes) has demonstrated considerable potential for the treatment of a variety of diseases. However, progress toward clinical application is often delayed by the lack of reliable and scalable mixing of components sufficient to guarantee consistent performance in vivo. Attempts to improve and standardize mixing have been limited by the sensitivity of pDNA to shear-related degradation. Here we describe a simple pneumatic mixing device that enables the rapid and reproducible production of large volumes of nonviral gene therapy formulations and demonstrate its suitability for use with shear-sensitive pDNA.

引用

页码：666 / 668

页数：3

共 9 条

[1] Impact of plasmid supercoiling on the efficacy of a rabies DNA vaccine to protect cats [J].

Cupillard, L ;

Juillard, V ;

Latour, S ;

Colombet, G ;

Cachet, N ;

Richard, S ;

Blanchard, S ;

Fischer, L .

VACCINE, 2005, 23 (16) :1910-1916

[2] Aerosol delivery of robust polyethyleneimine-DNA complexes for gene therapy and genetic immunization [J].

Densmore, CL ;

Orson, FM ;

Xu, B ;

Kinsey, BM ;

Waldrep, JC ;

Hua, P ;

Bhogal, B ;

Knight, V .

MOLECULAR THERAPY, 2000, 1 (02) :180-188

[3] A concentrated and stable aerosol formulation of cationic Lipid: DNA complexes giving high-level gene expression in mouse lung [J].

Eastman, SJ ;

Lukason, MJ ;

Tousignant, JD ;

Murray, H ;

Lane, MD ;

StGeorge, JA ;

Akita, GY ;

Cherry, M ;

Cheng, SH ;

Scheule, RK .

HUMAN GENE THERAPY, 1997, 8 (06) :765-773

[4] Increased persistence of lung gene expression using plasmids containing the ubiquitin C or elongation factor 1α promoter [J].

Gill, DR ;

Smyth, SE ;

Goddard, CA ;

Pringle, IA ;

Higgins, CF ;

Colledge, WH ;

Hyde, SC .

GENE THERAPY, 2001, 8 (20) :1539-1546

[5]

HATTORI Y, 2005, EVALUATION SIZE ZETA, P293

[6] Simple mixing device to reproducibly prepare cationic lipid-DNA complexes (lipoplexes) [J].

Hirota, S ;

de Ilarduya, CT ;

Barron, LG ;

Szoka, FC .

BIOTECHNIQUES, 1999, 27 (02) :286-+

[7] Shear-induced degradation of plasmid DNA [J].

Lengsfeld, CS ;

Anchordoquy, TJ .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2002, 91 (07) :1581-1589

[8] Effect of shear on plasmid DNA in solution [J].

Levy, MS ;

Collins, IJ ;

Yim, SS ;

Ward, JM ;

Titchener-Hooker, N ;

Shamlou, PA ;

Dunnill, P .

BIOPROCESS ENGINEERING, 1999, 20 (01) :7-13

[9]

PERRY RH, 1986, PERRYS CHEM HDB

← 1 →