LIPOSOME-MEDIATED GENE-TRANSFER AND EXPRESSION VIA THE SKIN

被引:102
作者
ALEXANDER, MY [1 ]
AKHURST, RJ [1 ]
机构
[1] UNIV GLASGOW,YORKHILL HOSP,DEPT MED GENET,GLASGOW G3 8SJ,LANARK,SCOTLAND
基金
英国惠康基金;
关键词
D O I
10.1093/hmg/4.12.2279
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A beta-galactosidase gene expression construct was used to investigate the effectiveness of gene delivery and expression when DNA/liposome complexes were topically applied to mouse skin in vivo. DNA was complexed with a commercial preparation of N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethyl-ammoniummethyl-sulphate (DOTAP) in a ratio of 1:1.6 (w/w). The DNA rapidly penetrated the skin and was expressed in the epidermis, dermis and hair follicles. A DNA concentration of 267 mu g/ml DNA was found to be optimal for efficient transfection. Expression was seen as early as 6 h post-application, persisted at high levels 24 and 48 h post-treatment, but was markedly reduced by 7 days after application. In conclusion, utilising a commercially available liposome preparation, topically-applied DNA/liposome complexes can be efficiently delivered and expressed in several cell types within the skin. This simple, non-invasive technique may have implications for a number of gene therapy applications.
引用
收藏
页码:2279 / 2285
页数:7
相关论文
共 25 条
[1]   CIRCULATING HUMAN FACTOR-IX PRODUCED IN KERATIN PROMOTER TRANSGENIC MICE - A FEASIBILITY STUDY FOR GENE-THERAPY OF HEMOPHILIA-B [J].
ALEXANDER, MY ;
BIDICHANDANI, SI ;
COUSINS, FM ;
ROBINSON, CJM ;
DUFFIE, E ;
AKHURST, RJ .
HUMAN MOLECULAR GENETICS, 1995, 4 (06) :993-999
[2]   SKIN HYPERKERATOSIS AND PAPILLOMA FORMATION IN TRANSGENIC MICE EXPRESSING A RAS ONCOGENE FROM A SUPRABASAL KERATIN PROMOTER [J].
BAILLEUL, B ;
SURANI, MA ;
WHITE, S ;
BARTON, SC ;
BROWN, K ;
BLESSING, M ;
JORCANO, J ;
BALMAIN, A .
CELL, 1990, 62 (04) :697-708
[3]  
BEDDINGTON RSP, 1989, DEVELOPMENT, V106, P37
[4]   LIPOSOME-MEDIATED CFTR GENE-TRANSFER TO THE NASAL EPITHELIUM OF PATIENTS WITH CYSTIC-FIBROSIS [J].
CAPLEN, NJ ;
ALTON, EWFW ;
MIDDLETON, PG ;
DORIN, JR ;
STEVENSON, BJ ;
GAO, X ;
DURHAM, SR ;
JEFFERY, PK ;
HODSON, ME ;
COUTELLE, C ;
HUANG, L ;
PORTEOUS, DJ ;
WILLIAMSON, R ;
GEDDES, DM .
NATURE MEDICINE, 1995, 1 (01) :39-46
[5]   THE GENETIC-BASIS OF EPIDERMOLYTIC HYPERKERATOSIS - A DISORDER OF DIFFERENTIATION-SPECIFIC EPIDERMAL KERATIN GENES [J].
CHENG, J ;
SYDER, AJ ;
YU, QC ;
LETAI, A ;
PALLER, AS ;
FUCHS, E .
CELL, 1992, 70 (05) :811-819
[6]   SYSTEMIC DELIVERY OF SECRETED PROTEIN BY GRAFTS OF EPIDERMAL-KERATINOCYTES - PROSPECTS FOR KERATINOCYTE GENE-THERAPY [J].
FENJVES, ES ;
SMITH, J ;
ZARADIC, S ;
TAICHMAN, LB .
HUMAN GENE THERAPY, 1994, 5 (10) :1241-1248
[7]   APPROACHES TO GENE-TRANSFER IN KERATINOCYTES [J].
FENJVES, ES .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1994, 103 (05) :S70-S75
[8]   SYSTEMIC DISTRIBUTION OF APOLIPOPROTEIN-E SECRETED BY GRAFTS OF EPIDERMAL-KERATINOCYTES - IMPLICATIONS FOR EPIDERMAL FUNCTION AND GENE-THERAPY [J].
FENJVES, ES ;
GORDON, DA ;
PERSHING, LK ;
WILLIAMS, DL ;
TAICHMAN, LB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :8803-8807
[9]   TOWARDS GENE-THERAPY FOR HEMOPHILIA-B USING PRIMARY HUMAN KERATINOCYTES [J].
GERRARD, AJ ;
HUDSON, DL ;
BROWNLEE, GG ;
WATT, FM .
NATURE GENETICS, 1993, 3 (02) :180-183
[10]   CYTOKINE GENE-EXPRESSION IN EPIDERMIS WITH BIOLOGICAL EFFECTS FOLLOWING INJECTION OF NAKED DNA [J].
HENGGE, UR ;
CHAN, EF ;
FOSTER, RA ;
WALKER, PS ;
VOGEL, JC .
NATURE GENETICS, 1995, 10 (02) :161-166