... adenovirus encoding brain-derived neurotrophic factor (Ad-BDNF) coinjected with a free radical scavenger, N-tert-butyl-(2-sulfoph-enyl)-nitrone (S-PBN), resulted in the survival of 63% axotomized ... Phosphorothioate-modified oli-godeoxyribonucleotides, III. NMR and UV spectroscopic studies of the Rp-Rp, Sp-SP, and Rp-Sp duplexes, [d(GGSAATTCC)]2, derived from diaster-eomeric O-ethyl phosphorothioates. ... Inc.2.GeneGunGeneguntransferofDNAhasbeensuccessfullyusedinplant,microbial,andmammaliancells(61).Inadditiontotheadvantageofnonimmunogeni-city,italsoprovidesgoodinvivogenetransferefficiencyandfocalgene delivery. Theprocessinvolvespenetrationofgold-coatedDNAparticlesintothetargetorganusinganelectricarcgeneratedbyhigh-voltagedis-chargethatacceleratesDNA-coatedparticlestohighvelocity(62).PlasmidDNAencodingnontoxicgreenfluorescentproteinwasdeliveredinrabbitcornea,andtherewasnoevidenceofcornealoroculardamage(63).IthasalsobeenshownthattheballistictransferofgenesforIL-4andCTLA-4inorthotopiccornealgraftinginBALB/cmicecausedprolongedgeneexpres-sionfor5days(64).Invitro,geneexpressingcorneaspecifickeratin12proteininTantigentransformedrabbitcornealepithelium(65).Sincethetargettissueistobesurgicallyexposed,thistechniquecanbeappliedtothesurfaceoftheeyeonly.3.LiposomesLiposomesaresphericalparticlescomposedofalipidbilayermembranethatencapsulatesapartofthesolvent.Dependingonthenatureoftheconcentriclayers,theyaredesignatedSUV(smallunilamellarvesicle;0.02–0:2m),LUV(largeunilamellarvesicle;0.1–0:5m),andLMV(largemultilamellarvesicle,0.1 10 m).Thesurfacecharacteristicsoflipo-somescanbemadeneutral,negative,orpositivelychargeddependingonthenatureoftheligandsonthesurface.Anumberoflipidshavebeenstudiedfordeliveryofgenetherapyproducts,butnosingletypehasbeenidentifiedasthemostsuitableforalltypesofgenedelivery(66).Theuseofplasmid-basedgeneexpressionislimitedbytheirsize(about3000kDa),hydrophi-licity,andalargenegativesurfacecharge(À30toÀ70mV)(67).Thesepropertiesinfluencethedistributioninthetissues,cellularuptake,andintra-cellulartraffickingofgenetherapydrugs(68).Itisnowacceptedthatcatio-niclipidsarenecessaryfordevelopmentofaliposomalformulationforgenetherapybecausethenegativechargeisahindrancetocellmembranetrans-port(69,70).Thenatureofthehydrophilicandhydrophobicpartsandthelinkersplaysanimportantrole,althoughthestructure-functionrelation-shipshavenotbeenestablished.Ontheotherhand,cationiclipids(Table2)cannotformliposomesaloneandarenormallyaccompaniedbyaneutrallipid...