GTMB 7 - Gene Therapy & Molecular Biology

Gene Therapy and Molecular Biology Vol 7, page 221Gene Ther Mol Biol Vol 7, 221-228, 2003Site-specific kidney-targeted plasmid DNA transferusing nonviral techniquesReview ArticleHiroki Maruyama 1 , Noboru Higuchi 1 , Shigemi Kameda 1 , Gen Nakamura 1 , JunichiMiyazaki 2 , and Fumitake Gejyo 11 Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences,1-757 Asahimachi-dori, Niigata 951-8120, Japan2 Division of Stem Cell Regulation Research, G6, Osaka University Medical School, 2-2 Yamadaoka, Suita 565-0871,Japan__________________________________________________________________________________*Correspondence: Hiroki Maruyama, MD, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School ofMedical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8120, Japan; Phone: +81-25-227-2194; Fax: +81-25-227-0775; E-mail: hirokim@med.niigata-u.ac.jpKey words: renal artery, renal vein, ureter, pelvis, glomerulus, tubules, interstitium, lipoplex, polyplex, hydrodynamic-basedtransfection, electroporation, ultrasound-microbubbleAbbreviations: hemagglutinating virus of Japan, (HVJ); anionic artificial viral envelope, (AVE); chloramphenicol acetyltransferase,(CAT); Epstein-Barr virus, (EBV); EBV nuclear antigen-1, (EBNA-1); transforming growth factor, (TGF)- β1; platelet-derived growthfactor, (PDGF)-B; N[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride, (DOTMA); cytomegalovirus, (CMV);dioleoylphosphatidyl ethanolamine, (DOPE); 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminiumtrifluoroacetate, (DOSPA), 3β-[N-(N,N-dimethylaminoethane)carbamoyl] cholesterol, (DAC-Chol); 3-dimethyl-hydroxyethylammoniumbromide, (DMRIE); Polyethyleneimine, (PEI); heat shock protein, (HSP); peritubular capillaries, (PTC); erythropoietin,(Epo); carbonic anhydrase, (CA); liposome-polycation-DNA complexes, (LPD)Received: 18 September 2003; Revised: 19 November 2003;Accepted: 25 November 2003; electronically published: November 2003SummaryKidney-targeted gene transfer has the potential to be one of the most important tools for broadening ourunderstanding of renal disease processes and for revolutionizing the treatment of renal diseases. We reviewed theliterature on kidney-targeted plasmid DNA transfer using nonviral techniques: naked plasmid DNA, cationiclipid/DNA complex, hemagglutinating virus of Japan (HVJ)-liposome complex, anionic artificial viral envelope-typeHVJ-liposome complex, cationic polymer/DNA complex, electroporation, ultrasound-microbubble, andhydrodynamics-based transfection. Gene-transfer methods using nonviral techniques are administered via renalarterial, renal venous, pelvic, ureteric, or direct routes into the glomerulus, tubules, or interstitial fibroblasts. Genetransfer can be achieved with varying degrees of transfection efficiency and duration of gene expression. Thus, wecan select the most effective gene transfer technique to deliver the appropriate therapeutic gene to the particularsites involved in various renal diseasesI. IntroductionWe can access the kidney by four different localroutes: the renal artery, anterogradely; the renal vein,retrogradely; the urinary tract (ureter or pelvis),retrogradely; and by direct injection.Viruses (adenovirus, adeno-associated virus,retrovirus and others) are used as a vector to transferexogenous genes into kidneys. Although these vectors canachieve high gene transfer efficiency, it is still possiblethat the protein encoded by viral genes induceimmunological responses. On the other hand, nonviraltechniques have several advantages over transfer usingviral vectors. A large quantity of highly purified plasmidDNA is easily and inexpensively obtained. Because thereare fewer size constraints than with current viral vectors,plasmid vectors can carry larger genes. Plasmid vectorsare less likelihood of inducing an immunological responsethan with viral vectors.The local route to the kidney and the kind of nonviraltechniques used principally determine the transgeneexpression sites (Tomita et al, 1992; Isaka et al, 1993;Akami et al, 1994; Arai et al, 1995; Boletta et al, 1997; Laiet al, 1997, 1998; Tsujie et al, 2000; Foglieni et al, 2000;Tsujie et al, 2001a, 2001b; Maruyama et al, 2002a; Lan etal, 2003; Kita et al, 2003). Tubules have been targeted bythe injection of naked plasmid DNA into the intra-renalparenchyma (Lai et al, 1997), cationic lipid/DNA complex221