References on the Use of ALZET® Osmotic Pumps in Gene Therapy

P8852 Wang,H.Y., Ghosh,A., Baigude,H., Yang,C.S., Qiu,L.H., Xia,X.G., Zhou,H.X., Rana,T.M., Xu,Z.S. Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression. Journal of Biological Chemistry 2008; 283(-23-):15845-15852. >>> RNA, small interfering, modified; RNA, small interfering; PBS; CSF/CNS (intrathecal, subarchanoid space); Mice (transgenic); 1007D; 2004; 7, 28 days; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (Fig. 3); no stress (see pg. 15846, 15849); stability verified by 28 days invivo (see Fig. 2); half-life (p. 15846) "short"; gene therapy; brain tissue distribution; animal info (SOD1G93A Tg); neurodegenerative (ALS); mp + catheter positioning confirmed; Target (SOD1); "when infused at disease onset at the therapeutic dose for 4 weeks, this siRNA slows disease progression without detectable adverse effects.".

P8865 Kobayashi,M., Okada,T., Murakami,T., Ozawa,K., Kobayashi,E., Morita,T. Tissue-targeted in vivo gene transfer coupled with histone deacetylase inhibitor depsipeptide (FK228) enhances adenoviral infection in rat renal cancer allograft model systems. UROLOGY 2007; 70(-6-):1230-1236. >>> Ganciclovir; IP; Rat; 7 days; Gene therapy; animal info (male, ACI, 6-8 wks old).

P8510 Djalilian,H.R., Caicedo,E., Lessan,K., Grami,V., Le,C.T., Spellman,S.R., Pambuccian,S., Hall,W.A., Low,W.C., Ondrey,F.G. Efficacy of an osmotic pump delivered, GM-CSF-based tumor vaccine in the treatment of upper aerodigestive squamous cell carcinoma in rats. CANCER IMMUNOLOGY IMMUNOTHERAPY 2007; 56(-8-):1207-1214. >>> Granulocyte macrophage-colony stimulating factor, murine; interleukin-12; PBS; SC; Rat; 28 days; Controls received mp w/ vehicle; dose-response (fig 1); no stress (see pg. 1209); cancer (upper aerodigestive tract carcinoma); peptides; animal info (Fisher 344, 125-150 g); good methods; "This latter method (mp) has several advantages. First, the use of minipumps obviates the cumbersome need to transfect tumor cells and completely characterize their cytokine repertoires. Second, it allows for independent and rigorous control over the kinetics of administration of cytokine and antigen dosages. Third, it may generate les controversy than those techniques requiring "gene therapy" IRB approval." (p. 1213)..

P8110 Iwasaki,Y., Ueda,M., Yamada,T., Kondo,A., Seno,M., Tanizawa,K., Kuroda,S., Sakamoto,M., Kitajima,M. Gene therapy of liver tumors with human liver-specific nanoparticles. Cancer Gene Therapy 2007; 14(-1-):74-81. >>> Ganciclovir; Water, sterile; SC; Rat (nude); 12 days; Controls received mp w/ agent and plasmid w/out gene therapy gene; no stress (see p.78); cancer (liver); gene therapy; animal info (male, F344/N, nu/nu, 5 wks old, 180g., NuE hepatic tumors); GCV acts as pro-drug for HSV-tk expression plasmid gene therapy.

R0239 Richardson,R.T., Noushi,F., O'Leary,S. Inner ear therapy for neural preservation. AUDIOLOGY AND NEURO-OTOLOGY 2006; 11(-6-):343-356. >>> Nerve groth factor; NT-3; adenovirus; brain-derived neurotrophic factor; perilymph, artificial; glial-derived neurotrophic factor; ciliary neurotrophic factor; fibroblast growth factor, acidic; fibroblast growth factor-1; fibroblast growth factor-2; fibroblast growth factor, basic; Ear (cochlea); ear (scala tympani); Guinea-pig; 1,2,4,8 weeks; 15-60, 11-12, 26 days; Comparison of polymers, hydrogels, gene therapy, cell-based therapy, and injections vs. mp; long-term study; pumps replaced; no stress (see pg. 350); half-life (p. 344), short in blood; gene therapy; peptides; animal info (deafened); Table 2; "The mini-osmotic pump device is ideally suited to studying the effects of neurotrophic factors in the cochlea experimentally." (p. 350).

P7936 Bondanza,A., Valtolina,V., Magnani,Z., Ponzoni,M., Fleischhauer,K., Bonyhadi,M., Traversari,C., Sanvito,F., Toma,S., Radrizzani,M., La Seta-Catamancio,S., Ciceri,F., Bordignon,C., Bonini,C. Suicide gene therapy of graft-versus-host disease induced by central memory human T lymphocytes. Blood 2006; 107(-5-):1828-1836. >>> Ganciclovir; SC; Mice (SCID); 2001; 7 days; Controls received mp w/ saline; animal info (female, NOD/SCID, 6-8 weeks old, GvHD); gene therapy.

P7495 Burchardt,M., Burchardt,T., Anastasiadis,A.G., Buttyan,R., de la Taille,A., Shabsigh,A., Frank,J., Shabsigh,R. Application of angiogenic factors for therapy of erectile dysfunction: protein and DNA transfer of VEGF 165 into the rat penis. UROLOGY 2005; 66(-3-):665-670. >>> Vascular endothelial growth factor, human 165; Saline, sterile; heparin; IA (renal); Rat; 2004; 28 days; Controls received mp w/ vehicle; functionality of mp verified by VEGF serum immunoassay; comparison of CDNA plasmid micro-injections vs. mp; gene therapy; peptides; animal info (male, Sprague-Dawley); urology; 2000 Units of heparin used.

P7393 Thakker,D.R., Natt,F., Huesken,D., van der Putten,H., Maier,R., Hoyer,D., Cryan,J.F. siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain. Molecular Psychiatry 2005; 10(-8-):782-789. >>> RNA, small interfering; citalopram; RNA, mm; RNAi buffer, isotonic; CSF/CNS; Mice; 1002; 2 weeks; Controls received mp w/ vehicle; gene therapy; downregulation of SERT; animal info (male, BALB/C, 19-29 g); "maximally effective RNAi response requires 2 weeks of siRNA infusion." P. 783; behavioral study.

P7335 Yin,H., Chao,L., Chao,J. Kallikrein/kinin protects against myocardial apoptosis after ischemia/reperfusion via Akt-glycogen synthase kinase-3 and Akt-Bad.14-3-3 signaling pathways*. Journal of Biological Chemistry 2005; 280(-9-):8022-8030. >>> Virus, adeno-associated; cytomegalovirus promoter; IP; Rat; ; Cardiovascular; gene therapy; adenoviral vector harboring the human tissue kallikrein cDNA (ad. CMV-TK).

P7248 Lakka,S.S., Gondi,C.S., Dinh,D.H., Olivero,W.C., Gujrati,M., Rao,V.H., Sioka,C., Rao,J.S. Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas. Journal of Biological Chemistry 2005; 280(-23-):21882-21892. >>> RNA, small interfering; RNA, small interfering, uPAR; RNA, small interfering, MMP-9; CSF/CNS; Mice (nude); 1002; 2 weeks; Controls received mp w/ PBS or empty vector; cancer (glioblastoma); siRNA is within a plasmid vector (pUM vector); antiangiogenesis; gene therapy.

P6992 Wolfe,D., Niranjan,A., Trichel,A., Wiley,C., Ozuer,A., Kanal,E., Kondziolka,D., Krisky,D., Goss,J., DeLuca,N., Murphey-Corb,M., Glorioso,J.C. Safety and biodistribution studies of an HSV multigene vector following intracranial delivery to non-human primates. Gene Therapy 2004; 11(-23-):1675-1684. >>> Ganciclovir; SC; Monkey (Rhesus); 2ML1; 2ML2; 4,5,34,35 days; Pumps replaced after 2 weeks; no stress (see pg. 1677); cancer (glioblastoma); toxicology; MRI; multiple pumps per animal (2); gene therapy.

P6769 Thakker,D.R., Natt,F., Huesken,D., Maier,R., Mueller,M., van der Putten,H., Hoyer,D., Cryan,J.F. Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2004; 101(-49-):17270-17275. >>> RNA, small interfering; GBR 12909; RNAi buffer; CSF/CNS (dorsal third ventricle); Mice; 1007D; 1002; 1,2 weeks; Controls received mp w/ vehicle; antisense (EGFP, DAT, scrambled sequence); Plastics One cannula used; "Results highlight the temporal effects of siRNA, requiring a constant minipump-mediated infusion in the dorsal third ventricle for a stable and bilateral knockdown of gene expression in the brain." (p. 17275); gene therapy.

P6720 Gondi,C.S., Lakka,S.S., Dinh,D.H., Olivero,W.C., Gujrati,M., Rao,J.S., Rao,J.S. RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas. ONCOGENE 2004; 23(--):8486-8496. >>> RNA, small interfering; EV/SV vector; PBS; CSF/CNS (intratumoral); Mice (nude); ; Controls received mp w/ vehicle; tissue perfusion (tumor); cancer (glioma); gene therapy; antiangiogenesis; siRNA (cathepsin B); pump model not stated (0.25 ul/hr); "...local intracranial delivery of pcu using mini-osmotic pumps effectively inhibited human malignant glioma growth.".

P6618 Lakka,S.S., Gondi,C.S., Yanamandra,N., Olivero,W.C., Dinh,D.H., Gujrati,M., Rao,J.S. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. ONCOGENE 2004; 23(-27-):4681-4689. >>> RNA, small interfering; human cytomegalovirus promoter; Empty vector; CSF/CNS; Mice; 2004; 5 weeks; Cancer (glioblastoma); siRNA against mmp-9 and cathepsin; antiangiogenesis; gene therapy.

P5995 Dorn,G., Patel,S., Wotherspoon,G., Hemmings-Mieszczak,M., Barclay,J., Natt,F.J.C., Martin,P., Bevan,S., Fox,A., Ganju,P., Wishart,W., Hall,J. siRNA relieves chronic neuropathic pain. NUCLEIC ACIDS RESEARCH 2004; 32(-5-):1-6. >>> RNA, small interfering; oligonucleotide, antisense; Saline; CSF/CNS (intrathecal); Rat; 6-7 days; Controls received mp w/ missense siRNA; no stress (see pg. 4); antisense (P2X3); gene therapy; siRNA (P2X3); pain research.

P5966 Roguin,A., Avivi,A., Nitecki,S., Rubinstein,I., Levy,N.S., Abassi,Z.A., Resnick,M.B., Lache,O., Melamed-Frank,M., Joel,A., Hoffman,A., Nevo,E., Levy,A.P. Restoration of blood flow by using continuous perimuscular infiltration of plasmid DNA encoding subterranean mole rat Spalax ehrenbergi VEGF. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES O F AMERICA 2003; 100(-8-):4644-4648. >>> DNA, naked; vascular endothelial growth factor, DNA; Water; IM; Mice; 2001; 7 days; Controls received mp w/ saline; tissue perfusion (quadriceps muscle); gene therapy; fenestrated catheter; pump implanted IP; "we have shown that when using plamid DNA, continuous administration is superior to multiple simultaneous IM injections." (p. 4647).

P5657 Herraiz,M., Beraza,N., Solano,A., Sangro,B., Montoya,J., Qian,C., Prieto,J., Bustos,M. Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mito chondrial DNA depletion. Human Gene Therapy 2003; 14(-5-):463-472. >>> Ganciclovir; Saline; IP; Rat; 2ML2; 3,7,10 days; Controls received mp w/ saline; gene therapy.

P5520 Melton,L.M., Keith,A.B., Davis,S., Oakley,A.E., Edwardson,J.A., Morris,C.M. Chronic glial activation, neurodegeneration, and APP immunoreactive deposits following acute administration of double-stranded RNA. Glia 2003; 44(-1-):1-12. >>> RNA, double stranded; statolon dsRNA; polyinosinic acid ds RNA; polycytidilic acid dsRNA; Tris/borate/EDTA buffer; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ vehicle; gene therapy; post op. care (buprenorphine); statolon is a naturally occuring dsRNA from a mycophage; neurodegenerative (Parkinson's disease, Alzheimer's); "we have found that intracerebral administration of dsRNA from an.

R0213 Duan,M.L., Ulfendahl,M., Laurell,G., Counter,A.S, Pyykko,I., Borg,E., Rosenhall,U. Protection and treatment of sensorineural hearing disorders caused by exogenous factors: experimental findings and potential clinical application. Hearing Research 2002; 169(--):169-178. >>> Liposomes, cationic; Ear (cochlea); Guinea-pig; ; Gene therapy; tissue perfusion (cochlea).

R0183 Lalwani,A.K., Jero,J., Mhatre,A.N. Developments in cochlear gene therapy. GENETIC HEARING IMPAIRMENT: ITS CLINICAL PRESENTATIONS 2002; 61(-;-):28-33. >>> ; Ear; ; Gene therapy; review of gene vectors and routes of delivery for cochlear gene therapy; tissue perfusion (cochlea).

R0164 Lalwani,A.K., Jero,J., Mhatre,A.N. Current issues in cochlear gene transfer. Audiol.Neurootol. 2002/5; 7(-3-):146-151. >>> Gene vectors; Ear (cochlea); Guinea-pig; 1007D; ; Gene therapy; review of various cochlear gene delivery methods; diagram of the various delivery methods (p. 147); tissue perfusion (cochlea).

P6179 Mittoux,V., Quary,S, Monville,C, Lisovoski,F, Poyot,T, Conde,F., Escartin,C., Robichon,R  Journal of Neuroscience 2002; 22(-11-):4478-4486. >>> Nitropropionic acid, 3-; Water, deionized; NaOH; SC; Rat; 2ML4; 5,16 days; Controls received mp w/ nothing; gene therapy; neurodegenerative (Huntington's disease); behavioral testing; 3NP had a pH of 7.4.

P6138 Smoot,L.M., McCormick,J.K., Smoot,J.C., Hoe,N.P., Strickland,I., Cole,R.L., Barbian,K.D., Earhart,C.A., Ohlendorf,D.H., Veasy,L.G., Hill,H.R., Leung,D.Y.M., Schlievert,P.M., Musser,J.M. Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks. Infection and Immunity 2002; 70(-12-):7095-7104. >>> rSpeL; rSpeM; rSpeC; PBS; SC; Rabbit; 15 days; rSpeL,M and C are bacteriophage genes; gene therapy; "The miniosmotic pump model of STSS was also used to assess the lethality of rSpeL and rSpeM, since these devices release a constant amount of exotoxin into subcutaneous tissue and hence resemble infection with exotoxin-producing GAS.".

P5596 Doetsch,F., Petreanu,L., Caille,I., Garcia-Verdugo,J.M., Alvarez-Buylla,A. EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 2002; 36(-6-):1021-1034. >>> Epidermal growth factor; Ganciclovir; Saline; BSA; PBS; CSF/CNS; Mice; 1007D; 1002; 7 hours; 6 days; Controls received mp w/ vehicle; Gene therapy; peptides; EGF was diluted in BSA-containing saline and infused for 7 hours, or 6 days in 1007D pumps; Ganciclovir was diluted in PBS and infused for 6 days via 1002 pumps.

P5540 Lalwani,A.K., Han,J.J., Castelein,C.M., Carvalho,G.J., Mhatre,A.N. In vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. Laryngoscope 2002; 112(-8-):1325-1334. >>> Virus, adeno-associated; Gene, green fluorescent protein; Gene, brain-derived neurotrophic factor; PBS; Ear (cochlea); Guinea-pig; 1007D; 1 week; Gene therapy; cochlea cannulated with PE10 attached to PE50; virus contained gene for brain-derived neurotrophic factor and/or green fluorescent protein; tissue perfusion (cochlea).

R0184 Jacobs,A, Voges,J, Reszka,R., Lercher,M, Gossmann,A, Kracht,L  Lancet 2001; 358(--):727-729. >>> ; Rat; ; Gene therapy; brief references to minipump-infusion study (p. 728) on non-viral vector administration into rat F98 gliomas with subsequent ganciclovir treatment.

P7117 Luebke,A.E., Foster,P.K., Muller,C.D., Peel,A.L. Cochlear function and transgene expression in the guinea pig cochlea, using adenovirus and adeno-associated virus-directed gene transfer. Human Gene Therapy 2001; 12(--):773-781. >>> Adenovirus vector; virus, adeno-associated; Perilymph, artificial; Ear (scala tympani); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle, and no treatment to contralateral ear; no stress (see pg. 778); good methods; gene therapy; cyanoacrylate adhesive; tissue perfusion (scala tympani).

P4821 Luebke,A.E., Steiger,J.D., Hodges,B.L., Amalfitano,A. A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function.. Gene Therapy 2001; 8(--):789-794. >>> Methylisothiourea,S-; Adenovirus vector; Gene, mouse iNOS cDNA sequence; Saline; Dye, methlene blue; Dye, India black ink; PBS; SC (wound healing site);; rat;; 2001; 2ML1;; ; Controls received mp w/ saline; functionality of mp verified by dye infusion; gene therapy; enzyme inhibitor; methylisothiourea,S- is an inducible nitric oxide synthase inhibitor (iNOS inhibitor); wound healing; SC-implanted pumps infused 2 hydroxyproline sponges via catheter; initial studies used 2ML1 pumps to infuse dyes in order to assess the feasibility of direct infusion with pumps; iNOS inhibitor infusion was with 2001 pumps; pumps were designed to infuse directly into SC implanted polyvinyl sponges at the wound site; Adenovirus vector was dissolved in PBS; iNOS inhibitor was delivered in saline; diagram of pump-catheter assembly and location (p. 18); "Dye infusion demonstrated both grossly and microscopically excellent delivery of the infusate to wound sponges" (p. 18);.

P5767 Reynolds,S.D., Hong,K.U., Giangreco,A., Mango,G.W., Guron,C., Morimoto,Y., Stripp,B.R. Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol 2000; 278(-6-):L1256-L1263. >>> Ganciclovir; Saline; Mice (transgenic); 6,12 days; Controls received mp w/ vehicle; gene therapy.

P4580 Bush,T.G, Puvanachandra,N, Horner,C.H, Polito,A, Ostenfeld,T, Svendsen,C.N, Mucke,L, Johnson,M.H, Sofroniew,M.V  Neuron 1999/6; 23(--):297-308. >>> Ganciclovir; memantine; Saline, sterile physiological; SC; Mice (transgenic); 7, 14 days; gene therapy; ganciclovir infused for 7 days; memantin infused for 14 days.

P4471 Han,J.J, Mhatre,A.N., Wareing,M, Pettis,R, Gao,W.-Q., Zufferey,R.N, Trono,D, Lalwani,A.K. Transgene expression in the guinea pig cochlea mediated by a lentivirus-derived gene transfer vector.. Human Gene Therapy 1999/7/20; 10(--):1867-1873. >>> Lentivirus; gene, green fluorescent protein; Saline; PBS;; ear (cochlea);; guinea-pig;; 1007D;; 8, 3 days;; controls received mp w/vehicle; tissue perfusion (scala tympani); gene therapy;.

P4436 Wareing,M, Mhatre,A.N, Pettis,R, Han,J.J, Haut,T, Pfister,M.H.F, Hong,K, Zheng,W.W, Lalwani,A.K  Hearing Research 1999; 128(--):61-69. >>> Liposomes, cationic; Gene, beta-galactosidase; Dextrose solution;; ear;; guinea-pig;; 1007D;; ; tissue perfusion (cochlea); comparison of micro injections vs. mp; stress/adverse reaction: significant fibrosis and acute immune response localized at the site of cochleostomy; gene therapy; prophylactic antibiotics provided; PE50 tubing was connected to PE10;.

P4579 Bush,T.G, Savidge,T.C, Freeman,T.C, Cox,H.J, Campbell,E.A, Mucke,L, Johnson,M.H, Sofroniew,M.V  Cell 1998/4/17; 93(--):189-201. >>> Ganciclovir;; Saline, sterile physiological; SC;; mice (transgenic); 2004; 2001; 2002; 1007D; 7, 14, 28 days; controls received no treatment; gene therapy.

P4028 Lalwani,A.K., Walsh,B.J., Reilly,P.G., Carvalho,G.J., Zolotukhin,S., Muzyczka,N., Mhatre,A.N. Long-term in vivo cochlear transgene expression mediated by recombinant adeno-associated virus. Gene Therapy 1998; 5(--):277-281. >>> Virus, adeno-associated; Gene, lacZ; Gene, green fluorescent protein; Saline; ear (cochlea); guinea-pig; no duration posted; controls received mp w/vehicle; tissue perfusion (cochlea); functionality of mp verified by gene expression; gene therapy.

P4027 Lalwani,A.K., Walsh,B.J., Carvalho,G.J., Muzyczka,N., Mhatre,A.N. Expression of adeno-associated virus integrated transgene within the mammalian vestibular organs. Am.J.Otology 1998; 19(--):390-395. >>> Virus, adeno-associated; Gene, green fluorescent protein; Gene, beta-galactosidase; PBS; ear (cochlea); guinea-pig; 1007D; 7 days; controls received mp w/vehicle, mp w/reporter gene, or no pump; tissue perfusion (scala tympani); gene therapy.

P4467 Cohen,J.L, Boyer,O, Salomon,B, Onclercq,R, Charlotte,F, Bruel,S, Boisserie,G, Klatzmann,D  Blood 1997/6/15; 89(-12-):4636-4645. >>> Ganciclovir;; PBS;; SC;; mice;; 2001;; 7 days;; controls received mp w/vehicle; functionality of mp verified by plasma levels; comparison of IP injections vs. mp; immunology; Gene therapy.

P3921 Benedetti,S., Dimeco,F., Pollo,B., Cirenei,B., Colombo,B.M., Bruzzone,M.G., Cattaneo,E., Vescovi,A., Didonato,S., Colombo,M.P., Finocchiaro,G. Limited efficacy of the hsv-tk/gcv system for gene therapy of malignant gliomas and perspectives for the combined transduction of the interleukin-4 gene. Human Gene Therapy 1997; 8(--):1345-1353. >>> Ganciclovir; Water; rat; mice (nude); 2002; 2ML2; 2 weeks; comparison of IP injections vs. mp; cancer; gene therapy.

P3859 Lalwani,A.K., Han,J.J., Walsh,B.J., Zolotukhin,S., Muzyczka,N., Mhatre,A.N. Green fluorescent protein as a reporter for gene transfer studies in the cochlea. Hear.Res. 1997; 114(--):139-147. >>> Virus, adeno-associated; Gene, green fluorescent protein; PBS; ear (cochlea); guinea-pig; 1007D; 2, 7 days; controls received mp w/saline or mp w/AAV-Bgal; tissue perfusion (scala tympani); good methods (p.141); gene therapy.

P3860 Zhu,J., Zhang,L., Hanisch,U.K., Felgner,P.L., Reszka,R. A continuous intracerebral gene delivery system for in vivo liposome-mediated gene therapy. Gene Therapy 1996; 3(--):472-476. >>> Liposomes; Gene, herpes simplex virus thymidine kinase; Gene, lacZ; CSF/CNS (caudate nucleus); Rat; 1003D; 3 days; controls received mp w/LacZ gene; tissue perfusion (tumor); functionality of mp verified by gene expression; comparison of intracerebral injections vs. mp; no stress (see pg.473); stability verified by gene expression; ALZET brain infusion kit used; cancer; gene therapy; "DNA-liposome complexes were stable within minipumps at body temperature (37C) for 1-3 days." (pg.474); "continuous administration of DNA-liposome complexes did not result in significant in vivo toxicity." (pg.474).

P3574 Franken,M., Estabrooks,A., Cavacini,L., Sherburne,B., Wang,F., Scadden,D.T. Epstein-barr virus-driven gene therapy for EBV-related lymphomas. Nature Medicine 1996; 2(-12-):1379-1382. >>> Ganciclovir; mice (SCID); 7 days; controls received p w/ saline; comparison of ip injections vs. mp; cancer; gene therapy.

P3410 Lalwani,A.K., Walsh,B.J., Reilly,P.G., Muzyczka,N., Mhatre,A.N. Development of in vivo gene therapy for hearing disorders: introduction of adeno-associated virus into the cochlea of the guinea pig. Gene Therapy 1996; 3(--):588-592. >>> Virus, adeno-associated, with bacterial gene seq; PBS; ear (cochlea); guinea-pig; 1007D; 2 weeks; controls received saline infusion; tissue perfusion (cochlea); Gene therapy.

P2284 Golumbek,P.T., Hamzeh,F.M., Jaffee,E.M., Levitsky,H., Lietman,P.S., Pardoll,D.M. Herpes simplex-1 virus thymidine kinase gene is unable to completely eliminate live, nonimmunogenic tumor cell vaccines. J.Immunother. 1992; 12(--):224-230. >>> Ganciclovir; SC; mice; 2002; 2-4 weeks; controls received mp w/vehicle; pumps replaced; immunology; Gene therapy.