GENE THERAPYDiseases for applying gene therapyDisease DefectTarget cell Severe combined Bone marrow cells or immunodeficiencyT-lymphocytesHemophiliaLiver, muscleCystic fibrosisLung CellsCancerMany cell typesNeuroloical diseasesParkinsons !l"heimers#erve Cells$nfectious %iseases!$D&, hepatitis B 'hite Bloo% Cells (ene therapy coul% )e very %ifferent for %ifferent %iseases*(ene transplantation +to patient with gene %eletion,*(ene correction+To revert specific mutation in the gene of interest,*(ene augmentation +to enhance e-pression of gene of interest,(ene therapyIn vivoEx vivo in vivo an% e- vivo schemeshttp://laxmi.nuc.ucla.edu:8237/M288/SChow_4_10/sld005.htmIN VIVOEX VIVO./ The genetic material is transferre% %irectly into the )o%y of the patient 0/ More or less ran%om process1 small a)ility to control1 less manipulations 2/ 3nly availa)le option for tissues that can not )e grown in vitro1 or if grown cells can not )e transferre% )ack !n vivo ene therapy./ The genetic material is first transferre% into the cells grown in vitro 0/ Controlle% process1 (enetically altere% cells are selecte% an% e-pan%e%1 more manipulations 2/ Cells are then returne% )ack to the patient Exvivo gene therapy$n4ections of nake% D#!Current attempts with nake% D#! vaccination in infectious %iseasesHIV HepatitisInfluenzaTuberculosis, Lye !isease"alaria#allistic $NA !n%ection &ene uns'Invente! for "N# transfer to plant cells$ully applicable to eu%aryotic cellsplasi! "N# sho&n here LiposomesNext level i!ea ' &hy na%e! "N#( Lets) &rap it in soething safeto increase transfection rateTherapeutic !rugsLipi!s ' are an obvious i!ea *D#! %elivery of genes )y liposomes+heaper than viruses No iune responseEspecially goo! for in,lung !elivery -cystic fibrosis.())*())) times more plasmid $NA needed for the same transfer efficiency as for viral vectorCystic fi)rosismost common lethal enetic disorder in Caucasian populations &( in +))) live births,' , Amon African and Asian is really rarea defect in the C-TR eneLungs create thic% ucus secretion-prone to infections, constant cough, lea!ing cause of !eath.Lungs in cystic fi)rosisNoral lung+$ lungsdilated crypts filled .ith mucus and bacteria, Normal alveolar appearance+$ lungs fille! &ith ucus lung !i! not collapse &hen it &as reove! postorte Cystic fi)rosis lungs are prone to infections!he "attle "etween #$C%s and "acte&ia lea!s ultiately to lung fibrosis an! !aage /Hyperinflammation/ and 0#C1s unable to eradicate bus2 instead damae lun tissue,"ucus protects bus"3ST C3""3N 4!RA5 4ECT3RSRetrovirusesHerpes simple6 virusescan create !ouble,stran!e! "N# copies of their /N# genoes0 +an integrate into genoe0 HIV for exaple!s"N# viruses that infect a neurons0 +ol! sores virus5etroviral vectors are a)le to infect %ivi%ing cells only1oo! for cancer gene therapy2o, retroviruses are ost often use! vectors for coon !isease gene therapy!n dividin cells nuclear membranes are bro7en do.n2 so viral enome can enter and interate into the chromosome 5eal treatments performe% with retroviral systemSe'e&e Com"ined (mmunodo)icienc* -2+I".3utation on +hroosoe 45 is often to blae'hat is &evere Com)ine% $mmuno%oficiency +&C$D,6 6 7 ne& ear infections per year6 4 serious sinus infections per year6 4 onth on antibiotics &ith little effect6 4 pneuonias per year ,, failure to gain &eight an! gro& ,, recurrent !eep s%in an! organ abscessesSC!$ treatmentsLife in germ-free envinronmentBone-marrow transplantations 7n"yme replacement therapy 8759 e-pensive1 not a cure1 temporary effect (7#7 T:75!P9