6/2/2014 Media Availability: Genetic Modification of Cells Proves Generally Safe as HIV Treatment Strategy

http://www.niaid.nih.gov/news/newsreleases/2014/Pages/CCR5mutation.aspx 1/2
NIAIDgranteeCarlH.June,M.D.,(center)ledthe
studywithcoinvestigatorsBruceL.Levine,Ph.D.,
(right)andPabloTebas,M.D.(left),allofthe
PerelmanSchoolofMedicineattheUniversityof
Pennsylvania,Philadelphia.
Credit:PennMedicine
Viewlargerimage.
NationalInstituteofAllergyand
InfectiousDiseases(NIAID)
http://www.niaid.nih.gov
FORIMMEDIATERELEASE
Wednesday,March5,2014
Additional
InformationFrom
NIAID
MediaContactInfo
NewsbyTopic
Health&ResearchTopics
MEDIAAVAILABILITY
GeneticModificationofCellsProvesGenerallySafeasHIV
TreatmentStrategy
NIHSupportedTechniqueMightHelpAchieveDrugFreeControl
ofHIV
WHAT:
Scientiststodayreportinitialresultsfromhumansonthesafetyand
tolerabilityofanovelstrategytocurbHIVdiseasebyremovingkey
cellsfromHIVinfectedindividuals,geneticallymodifyingthecellsto
resistHIVinfectionandreturningthemtothoseindividuals.Thebasic
andpreclinicalresearchonthisstrategy,whicheventuallymighthelp
peoplecontroltheviruswithoutdrugs,wasfundedbytheNational
InstituteofAllergyandInfectiousDiseases(NIAID),partoftheNational
InstitutesofHealth.ThePhaseIclinicaltrialwasfundedbySangamo
BioSciencesandwasledbyNIAIDgranteeCarlH.June,M.D.,withco
investigatorsBruceL.Levine,Ph.D.,andPabloTebas,M.D.,allofthe
PerelmanSchoolofMedicineattheUniversityofPennsylvania,
Philadelphia.

Thetrialbuiltontheobservationthatpeoplewhonaturallyhavea
geneticmodificationinaproteincalledCCR5areresistanttoHIV
infection,andwheninfectedwithHIV,progresstoAIDSmoreslowly.
CCR5isacellsurfacemolecule,orreceptor,thatmostHIVvariants
mustusetoentertheirprimarytarget:theCD4+Tcell.Inthetrial,CD4+Tcellswerecollectedfrom12HIV
infectedvolunteerswhoseviruswascontrolledbyantiHIVtherapy.Thesecellswerethentreatedinthelaboratory
withmoleculartoolscalledzincfingernucleases(ZFNs).TheZFNsweredesignedtosniptheDNAwithinthegene
thatcodesfortheCCR5receptor.ThisprocessintroducedageneticmutationrenderingCCR5receptorsnon
functional.Subsequently,thecellswerestimulatedtomultiply,andeachpatientreceivedaninfusionof10billionof
theirownCD4+Tcells,withroughlyafifthoftheCCR5genesnowmutated.
Fourweekslater,inaplannedinterruptionofantiHIVtherapy,halfthe
studyparticipantsstoppedtakingtheirantiretroviraldrugsfor8to12
weeks.Investigatorsfoundthattheexperimentaltreatmentwas
generallysafe,andthatthegeneticallymodifiedcellsappearedtobe
protectedfromHIVinfection.Inonevolunteerwhonaturallyhadthe
desiredmutationinhalfofhisCCR5genes,thevirusbecame
undetectableinhisbloodduringthe12weektreatmentinterruption.
Futureresearchwillincludeevaluatingthisexperimentaltreatmentin
morevolunteers,aswellasmaximizingthefrequencyofCCR5
disruptionbyZFNsandincreasingthepersistenceofthegenetically
modifiedcellsinthebodytoachieveatherapeuticeffect.

ARTICLE:
PTebasetal.GeneeditingofCCR5inautologousCD4Tcellsof
6/2/2014 Media Availability: Genetic Modification of Cells Proves Generally Safe as HIV Treatment Strategy
http://www.niaid.nih.gov/news/newsreleases/2014/Pages/CCR5mutation.aspx 2/2
Atechnicianremovesacaseofgeneticallymodified
CD4+Tcellsfromstorageinanultralow
temperaturefreezerforfinaltestingpriortoinfusion.
Credit:PennMedicine
Viewlargerimage.
LastUpdatedMarch05,2014
LastReviewedMarch04,2014
personsinfectedwithHIV.TheNewEnglandJournalofMedicineDOI:
10.1056/NEJMoa1300662(2014).

WHO:
NIAIDDirectorAnthonyS.Fauci,M.D.,isavailableforcomment.

CONTACT:
Toscheduleinterviews,pleasecontactLauraS.Leifman,(301)4021663,niaidnews@niaid.nih.gov.
NIAIDconductsandsupportsresearchatNIH,throughouttheUnitedStates,andworldwidetostudythecauses
ofinfectiousandimmunemediateddiseases,andtodevelopbettermeansofpreventing,diagnosingandtreating
theseillnesses.Newsreleases,factsheetsandotherNIAIDrelatedmaterialsareavailableontheNIAIDWebsite
atwww.niaid.nih.gov.
AbouttheNationalInstitutesofHealth(NIH):NIH,thenation'smedicalresearchagency,includes27Institutes
andCentersandisacomponentoftheU.S.DepartmentofHealthandHumanServices.NIHistheprimaryfederal
agencyconductingandsupportingbasic,clinical,andtranslationalmedicalresearch,andisinvestigatingthe
causes,treatments,andcuresforbothcommonandrarediseases.FormoreinformationaboutNIHandits
programs,visitwww.nih.gov.
NIH...TurningDiscoveryIntoHealth

backtotop
StayConnected: