Non-viral gene delivery: vehicle and delivery characterization

被引:0
作者
Lollo, CP [1 ]
Kwoh, DY [1 ]
Mockler, TC [1 ]
Ley, PM [1 ]
Guido, MS [1 ]
Coffin, CC [1 ]
Aleman, R [1 ]
Bartholomew, RM [1 ]
Carlo, DJ [1 ]
机构
[1] Immune Response Corp, Carlsbad, CA 92008 USA
关键词
in vivo; non-viral; gene delivery; characterization; serum inhibition;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The development of non-viral gene therapy has been hampered by an inability to reproducibly manufacture and characterize delivery system components and final formulations. Formation of interpolyelectrolyte complexes as the basis of various gene delivery methods has been approached as the first step towards development of synthetic viruses. We have found that preparation of interpolyelectrolyte complexes from disperse reagents gives a more homogeneous gene delivery vehicle than other methods. Methods which increase homogeneity also result in higher transfection efficiency in vivo. Expression levels of human growth hormone and other reporter proteins in mice confirm the potential of parenteral non-viral gene delivery for some therapeutic applications. Serum is demonstrated to inhibit transfection efficiency in vivo. Our results suggest that further development of methods to manufacture homogeneous disperse non-viral delivery vehicles with stealth characteristics may enhance both the potency and reproducibility of gene transfer in vivo.
引用
收藏
页码:S31 / S38
页数:8
相关论文
共 33 条
[1]   A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].
BOUSSIF, O ;
LEZOUALCH, F ;
ZANTA, MA ;
MERGNY, MD ;
SCHERMAN, D ;
DEMENEIX, B ;
BEHR, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301
[2]   FACTORS INFLUENCING RETROVIRAL-MEDIATED GENE-TRANSFER INTO HEPATOCYTES IN-VIVO [J].
BRANCHEREAU, S ;
CALISE, D ;
FERRY, N .
HUMAN GENE THERAPY, 1994, 5 (07) :803-808
[3]   CELLULAR AND HUMORAL IMMUNE-RESPONSES TO ADENOVIRAL VECTORS CONTAINING FACTOR-IX GENE - TOLERIZATION OF FACTOR-IX AND VECTOR ANTIGENS ALLOWS FOR LONG-TERM EXPRESSION [J].
DAI, YF ;
SCHWARZ, EM ;
GU, DL ;
ZHANG, WW ;
SARVETNICK, N ;
VERMA, IM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1401-1405
[4]   Light scattering in solutions [J].
Debye, P .
JOURNAL OF APPLIED PHYSICS, 1944, 15 (04) :338-342
[5]   GENE-THERAPY FOR HEMOPHILIA-A - PRODUCTION OF THERAPEUTIC LEVELS OF HUMAN FACTOR-VIII IN-VIVO IN MICE [J].
DWARKI, VJ ;
BELLONI, P ;
NIJJAR, T ;
SMITH, J ;
COUTO, L ;
RABIER, M ;
CLIFT, S ;
BERNS, A ;
COHEN, LK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (04) :1023-1027
[6]   REGULATION OF THE PHOSPHOENOLPYRUVATE CARBOXYKINASE HUMAN FACTOR-IX GENE INTRODUCED INTO THE LIVERS OF ADULT-RATS BY RECEPTOR-MEDIATED GENE-TRANSFER [J].
FERKOL, T ;
LINDBERG, GL ;
CHEN, J ;
PERALES, JC ;
CRAWFORD, DR ;
RATNOFF, OD ;
HANSON, RW .
FASEB JOURNAL, 1993, 7 (11) :1081-1091
[7]   DIRECT INVIVO GENE-TRANSFER TO AIRWAY EPITHELIUM EMPLOYING ADENOVIRUS POLYLYSINE DNA COMPLEXES [J].
GAO, L ;
WAGNER, E ;
COTTEN, M ;
AGARWAL, S ;
HARRIS, C ;
ROMER, M ;
MILLER, L ;
HU, PC ;
CURIEL, D .
HUMAN GENE THERAPY, 1993, 4 (01) :17-24
[8]   EFFICIENT GENE-TRANSFER INTO MYOCARDIUM BY DIRECT-INJECTION OF ADENOVIRUS VECTORS [J].
GUZMAN, RJ ;
LEMARCHAND, P ;
CRYSTAL, RG ;
EPSTEIN, SE ;
FINKEL, T .
CIRCULATION RESEARCH, 1993, 73 (06) :1202-1207
[9]   GENE-EXPRESSION FOLLOWING DIRECT-INJECTION OF DNA INTO LIVER [J].
HICKMAN, MA ;
MALONE, RW ;
LEHMANNBRUINSMA, K ;
SIH, TR ;
KNOELL, D ;
SZOKA, FC ;
WALZEM, R ;
CARLSON, DM ;
POWELL, JS .
HUMAN GENE THERAPY, 1994, 5 (12) :1477-1483
[10]   DNA COMPLEXES WITH POLYCATIONS FOR THE DELIVERY OF GENETIC MATERIAL INTO CELLS [J].
KABANOV, AV ;
KABANOV, VA .
BIOCONJUGATE CHEMISTRY, 1995, 6 (01) :7-20