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O E N E O E N E 1 H E R A P Y 1 H E R A P Y

A N A N O V E R V I E \ O V E R V I E \
Bubuk Numi
Scluk Lnivcrsit,
Scluklu Sclool
Ol Mcoicinc
Dcurtmcnt ol
Mcoicul Ocnctics
Kon,u/1LRKEY
z011
Vuat is Ceue tueraj: Vuat is Ceue tueraj:
What is Gene therapy?
- Cene Lherapy ls Lhe lnserLlon alLeraLlon or removal of
geneLlc maLerlal (unA or 8nA) wlLhln an lndlvlduals cells
or Llssues Lo LreaL dlsease or modlfy blologlcal funcLlons
- 1he Lerm gene Lherapy lncludes all Lechnlques used Lo
LreaL lnherlLed dlsorders lL can refer Lo Lwo dlfferenL
goals
- Lhe replacemenL of a defecLlve gene wlLh Lhe correcL
verslon
- expresslon of a Lransgene whose producL supplanLs lLs
defecLlve counLerparL
Vuat are tue ajjroacues Vuat are tue ajjroacues
o| eue tueraj: o| eue tueraj:
What are the approaches oI gene therapy?
- A normal gene may be lnserLed lnLo a nonspeclflc locaLlon
wlLhln Lhe genome Lo replace a nonfuncLlonal gene 1hls
approach ls mosL common
- 1he abnormal gene could be repalred Lhrough selecLlve
reverse muLaLlon whlch reLurns Lhe gene Lo lLs normal
funcLlon
- 1he regulaLlon (Lhe degree Lo whlch a gene ls Lurned on or
off) of a parLlcular gene could be alLered
ov does ov does
eue tueraj vork: eue tueraj vork:
ow does gene therapy work?
- ln mosL gene Lherapy sLudles a good" gene ls lnserLed lnLo
Lhe genome Lo replace an bad" gene
- 1here are a few ways Lo lnserL a good unA or 8nA lnslde Lhe
human body such as
NokeJ uNA lojectloo
vltol vectots
lbyslcol metboJs
cbemlcol metboJs
nybtlJ metboJs
47
tb
cbtomosome
ow does gene therapy work?
- 1he use of Lhe vlruses as Lhe vecLor has Lhe mosL promlslng
effecLs
1hese vlruses are alLered so LhaL when Lhey geL conLacL wlLh Lhe
cells of Lhe human Lhey coooot coose Jlseoses
- 1here are Lwo ways Lo use vlrus as Lhe vecLor
namely ln[ecLlng lL dlrecLly lnLo Lhe body and
by uslng an lnLravenous lnLo a parLlcular Llssue ln Lhe body where
Lhe lndlvldual cells wlll engulf Lhem
- 1he generaLlon of a funcLlonal proLeln producL from Lhe
LherapeuLlc gene resLores Lhe LargeL cell Lo a normal sLaLe
n SepLember 14 1990 researchers aL Lhe uS naLlonal
lnsLlLuLes of PealLh performed Lhe flrsL (approved) gene
Lherapy procedure on fouryear old AshanLl uesllva 8orn
wlLh a rare geneLlc dlsease called severe comblned lmmune
deflclency (SClu) she lacked a healLhy lmmune sysLem and
was vulnerable Lo every passlng germ
AshanLl's lymphocyLe cells don have AuA enzyme due Lo
muLaLlon ln Lhe relaLlve gene
ln AshanLls gene Lherapy procedure docLors removed whlLe
blood cells from Lhe chllds body leL Lhe cells grow ln Lhe
lab lnserLed Lhe mlsslng gene lnLo Lhe cells and Lhen
lnfused Lhe geneLlcally modlfled blood cells back lnLo Lhe
paLlenLs bloodsLream LaboraLory LesLs have shown LhaL Lhe
Lherapy sLrengLhened AshanLls lmmune sysLem she no
longer has recurrenL colds she has been allowed Lo aLLend
school and she was lmmunlzed agalnsL whooplng cough
W. French
Anderson
Kenneth.W
Culver
Michael
Blaese
ow Ashanti was treated?
- Severe Comblned lmmunodeflclency ulsease (SClu) ls due Lo a defecLlve gene for Adenoslne ueamlnase
(AuA) A reLrovlrus whlch ls capable of Lransferrlng lLs unA lnLo normal eukaryoLlc cells (LransfecLlon)
ls englneered Lo conLaln Lhe normal human AuA gene lsolaLed 1cell sLem llne cells from Lhe paLlenL are
exposed Lo Lhe reLrovlrus ln cell culLure and Lake up Lhe AuA gene 8elmplanLaLlon of Lhe Lransgenlc
cells lnLo Lhe paLlenLs bone marrow esLabllshes a llne of cells wlLh funcLlonal AuA whlch effeclLvely
LreaLs SClu.
Vuat are tue eue Vuat are tue eue
deiier metuods: deiier metuods:
What are the gene delivery methods?
nonvlral meLhods
- In[ect|on of Naked DNA 1hls ls Lhe slmplesL meLhod of nonvlral
LransfecLlon Cllnlcal Lrlals carrled ouL of lnLramuscular ln[ecLlon of
a naked unA plasmld have occurred wlLh some success
What are the gene delivery methods?
Ilral vecLors
- ketrov|ruses A class of vlruses LhaL can creaLe double
sLranded unA coples of Lhelr 8nA genomes 1hese coples of lLs
genome can be lnLegraLed lnLo Lhe chromosomes of hosL cells
Puman lmmunodeflclency vlrus (PlI) ls a reLrovlrus
- Adenov|ruses A class of vlruses wlLh doublesLranded unA
genomes LhaL cause resplraLory lnLesLlnal and eye lnfecLlons
ln humans 1he vlrus LhaL causes Lhe common cold ls an
adenovlrus
D|agram of a Adenov|rus
What are the gene delivery methods?
Ilral vecLors
- Adenoassoc|ated v|ruses A class of
small slnglesLranded unA vlruses LhaL
can lnserL Lhelr geneLlc maLerlal aL a
speclflc slLe on chromosome 19
- nerpes s|mp|ex v|ruses A class of
doublesLranded unA vlruses LhaL
lnfecL a parLlcular cell Lype neurons
Perpes slmplex vlrus Lype 1 ls a
common human paLhogen LhaL causes
cold sores
What are the gene delivery methods?
9hyslcal MeLhods
- L|ectroporat|on LlecLroporaLlon ls a meLhod LhaL uses shorL
pulses of hlgh volLage Lo carry unA across Lhe cell membrane
1hls shock ls LhoughL Lo cause Lemporary formaLlon of pores ln
Lhe cell membrane allowlng unA molecules Lo pass Lhrough
- More recenLly a newer meLhod of elecLroporaLlon Lermed
e|ectronava|anche transfect|on has been used ln gene Lherapy
experlmenLs 8y uslng a hlghvolLage plasma dlscharge unA was
efflclenLly dellvered followlng very shorL (mlcrosecond) pulses
Compared Lo elecLroporaLlon Lhe Lechnlque resulLed ln greaLly
lncreased efflclency and less cellular damage
What are the gene delivery methods?
9hyslcal MeLhods
- Sonoport|on uses ulLrasonlc frequencles Lo dellver unA lnLo
cells 1he process of acousLlc cavlLaLlon ls LhoughL Lo dlsrupL Lhe
cell membrane and allow unA Lo move lnLo cells
- Magnetofect|on ln a meLhod Lermed magneLofecLlon unA ls
complexed Lo magneLlc parLlcles and a magneL ls placed
underneaLh Lhe Llssue culLure dlsh Lo brlng unA complexes lnLo
conLacL wlLh a cell monolayer
What are the gene delivery methods?
9hyslcal MeLhods
- Gene Gun ln Lhls Lechnlque unA ls coaLed wlLh gold parLlcles
and loaded lnLo a devlce whlch generaLes a force Lo achleve
peneLraLlon of unA/gold lnLo Lhe cells
- Cene guns have been used unA Lransferrlng ln 9lanLs also Lo
dellver unA vacclnes ln Puman and anlmals
What are the gene delivery methods?
Chemlcal MeLhods
- L|posomes Llposomes are arLlflclally prepared veslcoles made of
llpld bllayer Llposomes can be used Lo dellver nuclelc aclds and
drugs for Cells
What are the gene delivery methods?
Chemlcal MeLhods
- Dendr|mers A dendrlmer ls a hlghly branched macromolecule
wlLh a spherlcal shape AnLlcancer drugs and nuclelc aclds
con[ugaLed on dendrlmers can be dellvered Lo cells
What are the gene delivery methods?
Pybrld meLhods
- V|resomes Lhey comblne llposomes wlLh an lnacLlvaLed vlral
vecLor llke PlI or lnfluenza vlrus
What are the gene delivery methods?
47
Lh
Chromosome
:man ArtiIicial chromosomes
(AC) might prove to be :seI:l
vectors Ior somatic gene
therapy. The I:nctional elements
oI s:ch an artiIicial
chromosome are telomeres, a
centromere and a replication
origin.
Vuat 1jes o| eue tueraj are: Vuat 1jes o| eue tueraj are:
Types oI gene therapy
- Cerm llne gene Lherapy
Cene Lherapy uslng germ llne cells (sperm eggs) resulLs
ln permanenL changes LhaL are passed down Lo
subsequenL generaLlons
- 1he Lwo maln meLhods of performlng germllne gene
Lherapy would be
1o LreaL a preembryo LhaL carrles a serlous geneLlc defecL
before lmplanLaLlon ln Lhe moLher wlLh Lhe use of lnvlLro
ferLlllzaLlon
1o LreaL Lhe germ cells (sperm or egg cells) of affllcLed
adulLs so LhaL Lhelr geneLlc defecLs would noL be passed on
Lo offsprlng approach Lo deleLe Lhe defecLlve gene and
lnserL a properly funcLlonlng replacemenL
- Some people vlew Lhls Lype of Lherapy as unnaLural and
llken lL Lo playlng Cod
Types oI gene therapy
- SomaLlc gene Lherapy
- SomaLlc cells are nonreproducLlve
- SomaLlc cell gene Lherapy uses Lhe lnserLlon of a normal gene lnLo Lhe
unA of somaLlc cells ln order Lo compensaLe for Lhe nonfuncLlonlng
defecLlve gene Whlch can be done ln a number of ways lncludlng
- lnserLlng Lhe gene lnLo any locaLlon wlLhln Lhe genome Lo replace a
nonfuncLlonal gene whlch ls Lhe mosL commonly used
- SwlLchlng Lhe abnormal gene for a normal gene Lhrough homologous
recomblnaLlon
- llxlng Lhrough selecLlve reverse muLaLlon whlch reLurns Lhe gene Lo lLs
normal funcLlon
Types oI gene therapy
In V|vo gene therapy
- 1he rooLs of Lhe Lerm ln vlvo glve us greaL lnslghL lnLo Lhe mechanlsm for Lhls process
lo vlvo means ln Lhe body ln LaLln
- ln Ilvo somaLlc gene Lherapy lnvolves Lhe lnLroducLlon of vecLors dlrecLly lnLo Lhe body
of Lhe person mosL usually lnLo Lhe affllcLed Llssue
- lor example lf Lhe alm was Lo LreaL skln cancer Lhe vecLors would be lnLroduced lnLo
Lhe melanoma lLself LvenLually Lhere ls hope LhaL vecLors wlll be found LhaL can be
lnLroduced dlrecLly lnLo Lhe bloodsLream however Lhere are dlfflculLles wlLh lmmune
sysLem response LhaL have slowed developmenL ln Lhls area Lo daLe
Lx V|vo gene therapy
- Colng back Lo our LaLln rooLs ex vlvo ls LranslaLed ouL of Lhe body
- LxIlvo somaLlc gene Lherapy ls dlfferenL from lnvlvo somaLlc gene Lherapy because of
Lhe locaLlon ln whlch Lhe cells are LreaLed
- ln exvlvo somaLlc gene Lherapy sclenLlsLs remove affllcLed cells from Lhe body expose
Lhem Lo vecLors and reLurn Lhe geneLlcally correcLed cells Lo Lhe lndlvldual 1hese
alLered cells Lhen repllcaLe and hopefully replace Lhe affllcLed cells
ln Ilvo gene Lherapy
Lx Ilvo gene Lherapy
Vuat diseases cau be cured vitu Vuat diseases cau be cured vitu
eue tueraj: eue tueraj:
Gene therapy in Severe Combined
Imm:ne DeIiciency (ADA-SCID)
- ls a auLosomal resseslve geneLlc dlsorder ln
whlch boLh 8 cells and 1 cells of Lhe adapLlve
lmmune sysLem are lmpalred due Lo a
defecL ln one of several posslble genes
- 1he lmmunodeflclency ls assoclaLed wlLh
SClu caused by adenoslne deamlnase (AuA)
gene muLaLlon
- 1he LherapeuLlc gene ls AuA was lnLroduced
lnLo Lhe bone marrow cells of such paLlenLs
ln Lhe laboraLory
:sc:lar Dystrophy
- When 8 yearold Andrew kllbarger of LancasLer hlo recelved Lhree ln[ecLlons
ln hls rlghL arm he became one of slx boys parLlclpaLlng ln Lhe flrsL uS gene
Lherapy Lrlal for muscular dysLrophy
- Andrew has uuchenne Muscular uysLrophy
- uMu paLlenLs lack Lhe gene LhaL conLrols producLlon of a proLeln called
dysLrophln whlch helps keep muscle cells lnLacL 9aLlenLs wlLh uMu usually
dle by Lhe age of 23 ofLen because of Lhe fallure of Lhe hearL and breaLhlng
muscles
Cystic Fibrosis
- ls a common recesslve geneLlc dlsorder whlch
affecLs Lhe enLlre body causlng progresslve
dlsablllLy and ofLen early deaLh
- Cl ls caused by a muLaLlon ln Lhe gene for Lhe
proLeln cysLlc flbrosls Lransmembrance
conducLance regulaLor (Cl18) 1hls gene ls
requlred Lo regulaLe Lhe componenLs of sweaL
dlgesLlve [ulces and mucus
- 1he baslc prlnclple of gene Lherapy ls Lo glve
paLlenLs coples of Lhe correct CI1k gene so Lhey
can make Lhe proLeln by synLhesls
emophilia
- 9aLlenLs born wlLh Pemophllla are noL
able Lo lnduce blood cloLs and suffer
from exLernal and lnLernal bleedlng
LhaL can be llfe LhreaLenlng
- luncLlonal genes capable of produclng
Lhe cloLLlng lacLor Ill and lacLor lx
were aLLached Lo an vlrus vecLors and
ln[ecLed lnLo Lhe 9aLlenL's llver Llssue.
Thalassemia
- sclenLlsLs are worklng Lo develop a gene Lherapy
LhaL may offer a cure for Lhalassemla 1hey are
currenLly looklng aL Lwo gene Lherapy LreaLmenLs
8eLaglobln gene and sLem cells
MedlcaLlons and feLal hemoglobln
Cancer
Sulclde gene Lherapy
- A sulclde gene ln geneLlcs wlll cause a cell Lo klll lLself Lhrough
apopLosls
- Sulclde gene Lherapy refers Lo Lransferrlng a sulclde gene llke p33
and caspase 8 Lo Lumor cell lead Lo cell deaLh
- Sulclde gene Lherapy assoclaLe acLlvaLlon a prodrug chemlcal ls
mosL frequenLly used sLraLegles for cancer gene Lherapy
1k gene
PSI vecLor
Cancer cell
lnfecLlon
Lxpresslon of 1k Lnzyme
nonLoxlc CCI
1oxlc CCI39
9hosphaLaLlon
Cancer
lmmunoLherapy
- deflned as LreaLmenL of dlseases by lnduclng enhanclng or
suppresslng an lmmune response
- ln Lhls sLraLegy lmmune response lnducer genes (llke lnLerleuklns)
dellver Lo Lumor cells wlLh Lhe alm Lo creaLe anLlcancer cyLolyses
lmmune response
ale inIertility
SclenLlsLs have used gene
Lherapy for Lhe flrsL Llme Lo
LreaL a form of lnferLlllLy 1he
breakLhrough ralses hopes LhaL
men who have Lhls problem
may one day be able Lo faLher
chlldren of Lhelr own
1he sclenLlsLs from yoto
uolvetslty and Lhe Notloool
lostltote of lofectloos ulseoses
ln !apan focused on a form of
ferLlllLy caused by Lhe fallure of
speclallsed cells ln Lhe LesLlcles
Lo keep sperm healLhy.
itochondrial diseases
W MlLochondrlal dlsorders are characLerlzed by proLeln
deflclencles affecLlng Lhe sLrucLure and funcLlon of
mlLochondrla 13 genes encoded by mLunA
W MosL currenL approaches Lo gene Lherapy of mlLochondrlal
dlseases alm aL expresslon of Lhe correcLlve mLunA
sequence
DNA vaccine
unA vacclnaLlon ls a novel
lmmunlzaLlon Lechnlque used by
ln[ecLlng geneLlcally englneerlng unA
Lo sLlmulaLe humoral and cellular
lmmune responses agalnsL dlseases
nuclelc acld vacclnes are sLlll
experlmenLal and have been applled
Lo a number of vlral bacLerlal
paraslLlc model of dlsease and
several cancer
S:rgery
Gene therapy has been
|nvest|gated |n many
aspects of p|ast|c and
reconstruct|ve surgery
1hese areas u|t|mate|y
|nvo|ve var|ous forms of
t|ssue hea||ng and the
man|pu|at|on of bony and
soft t|ssues to reconstruct
defects secondary to
neop|ast|c and congen|ta|
d|sorders and trauma
Diabetes
ne of Lhe posslble fuLure LreaLmenLs for
Lype 1 dlabeLes ls gene Lherapy
W 8esearchers have ldenLlfled a faulLy
gene whlch makes people wlLh Lhe gene
more llkely Lo develop Lype 1 dlabeLes ln
Lhe fuLure Lhls gene could be replaced by
a fullyworklng verslon of Lhe gene 1hls
could prevenL people from geLLlng
dlabeLes
W Pyun Chul Lee and Su!ln klm of ?onsel
unlverslLy ln Seoul korea and Lhelr
colleagues Lurned Lo geneLlc englneerlng
Lo produce an lnsulln analogue 1hey Lhen
lnserLed Lhe unA encodlng Lhls analogue
lnLo a vlrus LhaL had been rendered
harmless lncorporaLed Lhe reglon of Lhe
llver cell LhaL responds Lo glucose and
ln[ecLed Lhe modlfled vlrus lnLo dlabeLlc
mlce and raLs
IV
ln a feaL LhaL ls renewlng hopes for
conquerlng AluS researchers have
geneLlcally englneered paLlenLs vlLal
lmmune cells Lo make Lhem reslsLanL
Lo PlI lnfecLlon
1he CCk32 de|et|on mutat|on |n
the 1 ce|| chemok|ne receptor
assoclaLed wlLh PlI reslsLance.
!arkinson`s
Cene Lherapy for 9arklnsons dlsease has
moved a sLep closer wlLh uLlllze gluLamlc
acld decarboxylase (CAu) LhaL can
lmprove Lhe condlLlon of people wlLh Lhe
dlsease when ln[ecLed lnLo Lhelr bralns
1he gene Lherapy LreaLmenL lnvolved
sllpplng bllllons of coples of a gene lnLo
Lhe braln Lo calm overacLlve braln
clrculLry
An experlmenLal LreaLmenL for 9arklnson's
dlsease seemed Lo lmprove sympLoms
dramaLlcally so for one 39yearold man
wlLhouL causlng slde effecLs ln an early
sLudy of a dozen paLlenLs
A:toimm:ne diseases
1he app||cat|on of gene therapy
|n auto|mmune d|sease
represents a nove| use of th|s
techno|ogy 1he goa| of gene
therapy |n the treatment of
auto|mmune d|sease |s to
restore |mmune homeostas|s
by counter|ng the pro
|nf|ammatory effects of the
CD4
+
1 ce||s |n the |es|ons of
auto|mmun|ty
Alzheimer`s
ln 2001 Lhe flrsL
Alzhelmers paLlenLs
Lo LesL ploneerlng
gene Lherapy are
proof of Lhe
LreaLmenLs promlse
8raln lmaglng scans
showed slgnlflcanL
lncreases ln
meLabollc acLlvlLy ln
Lhe braln
besity
1here are many genes play role ln regulaLlon
of meLabollsm
ea:tiIication Bi gen tedavi yapp daha da
gzeIIesem harika oIur.
Bi trI sevgiIi buIamadm
Kendime yaa.
What are the challenges in gene therapy?
Is it saIe?
Challenges in gene therapy
V|ra| vectors uses of vlrus as vecLor ln gene Lherapy presenLs Lhe
followlng rlsks
lmmune response 1hls may cause lnflammaLlon LoxlclLy and ln severe
cases organ fallure
Ilral spread 8ecause vlruses can affecL more Lhan one Lype of cells lLs
posslble LhaL Lhe vlral vecLors may lnfecL cells ln addlLlon Lo Lhe ones for
whlch Lhey were lnLended [usL Lhose conLalnlng muLaLed or mlsslng genes
8everslon of Lhe vlrus Lo lLs orlglnal form lLs
posslble LhaL once lnLroduced lnLo Lhe body Lhe
vlruses may recover Lhelr orlglnal ablllLy Lo cause
dlsease
9osslblllLy of lnduclng a Lumor lf Lhe new genes geL
lnserLed ln Lhe wrong spoL ln Lhe genome Lhere ls a
chance LhaL Lhe lnserLlon mlghL lead Lo Lumor
formaLlon
Iesse Ge|s|nger (!une 18 1981
SepLember 17 1999) was Lhe flrsL person
publlcly ldenLlfled as havlng dled ln a
cllnlcal Lrlal for gene Lherapy Pe was 18
years old Celslnger suffered from
ornlLhlne Lranscarbamylase an xllnked
geneLlc dlsease of Lhe llver
Celslnger [olned a cllnlcal Lrlal run by Lhe
uolvetslty of leoosylvoolo LhaL almed aL
developlng a LreaLmenL for lnfanLs born
wlLh severe dlsease
n SepLember 13 1999 Celslnger was
ln[ecLed wlLh an adenovlral vecLor
carrylng a correcLed gene Lo LesL Lhe
safeLy of Lhe procedure Pe suffered a
masslve lmmune response Lrlggered by Lhe
use of Lhe vlral vecLor leadlng Lo mulLlple
organ fallure and braln deaLh Pe dled four
days laLer
Challenges in gene therapy
Destruct|on of norma| genes
ln common placemenL of LherapeuLlc
gene ln genome ls randomly
uellvered gene may can placed among
codlng reglon of a normal funcLlonal
gene and lead Lo newel muLaLlon 1hls
lssue can be lead Lo cancers
A 36yearold woman !olee
Mohr dled ln a Chlcago
hosplLal ln summer 2007
Lhree weeks afLer Laklng an
gene Lherapy for rheumaLold
arLhrlLls
Challenges in gene therapy
|eak|ng to reproduct|ve ce||s
ln vlvo somaLlc gene Lherapy for an
1lssue surroundlng reproducLlve
sysLem llke vary and uLerus
cancers ln women and 9rosLaLe ln
men capable spread of Lhe
LherapeuLlc gene(s) Lo reproducLlve
Llssue and sexual cells
could resulL ln geneLlc changes LhaL
could affecL chlldren you have afLer
LreaLmenL
Challenges in gene therapy
Gene Dop|ng
1he flrsL reporL LhaL gene Lherapy could
enhance muscle ln a mouse model was
publlshed afLer 2004 ALhena lymplc
Slnce Lhen lL has become of lncreaslng
concern LhaL some unscrupulous
aLhleLes may conslder gene Lherapy as a
vlable alLernaLlve Lo sLerold ln[ecLlon (a
Lerm called gene doplng) ln Lhe quesL Lo
enhance Lhelr aLhleLlc ablllLy
Cene doplng as deflned by Lhe World
AnLluoplng Agency (WAuA) ls Lhe
nonLherapeuLlc use of cells genes
geneLlc elemenLs or of Lhe modulaLlon
of gene expresslon havlng Lhe capaclLy
Lo lmprove aLhleLlc performance
1uauk ou er 1uauk ou er
mucu mucu
istory and development
1960 1970
- 1962 (Lederberg) 9osslblllLy of gene Lherapy ls speculaLed
- 1968 (8ogers and fuderer) Larly aLLempLs aL use of vlral vecLors
1970 1980
- 1970 (8alLlmore) ulscovery of reverse LranscrlpLase Copylng of 8nA lnLo
unA
- 1972 (lrledman and 8obln) SuggesLlon LhaL Lransformlng vlruses be used
for LherapeuLlc gene Lransfer
- 1973 (Craham and van der Lrb) Calclum phosphaLe LransfecLlon
- 1978 (Zamecnlk and SLephenson) llrsL use of an ollgonucleoLlde Lo acL as
lnhlblLor of LranslaLlon
istory and development
1980 1990
- 1984 (lzanL and WelnLraub) llrsL demonsLraLlon LhaL anLlsense nuclelc
acld can be used Lo downregulaLe gene expresslon
- 1987 (Poffman eL al) ldenLlflcaLlon of dysLrophln Lhe proLeln producL of
uuchene muscular dysLrophy gene (basls of fuLure gene Lherapy of Lhls
dlsorder)
- 1990 (8laese eL al) llrsL human gene Lherapy experlmenL CorrecLlon of
adenoslne deamlnase deflclency ln 1lymphocyLes uslng reLrovlral
medlaLed gene Lransfer
istory and development
1990 2000
- 1991 (Pazlnskl eL al) use of caLlonlc llposome for gene Lransfer ln
experlmenLal anlmals
- 1992 (Wells eL al) CorrecLlon of myopaLhy ln Lransgenlc mlce model of
uuchenne muscular dysLrophy by germllne gene Lransfer of human
dysLrophln uslng a reLrovlral vecLor
- 1993 (ldfleld and 8am) llrsL cllnlcal Lrlal of Perpes slmplex
vlrus/Lhymldlne klnase/ganclclovlr gene Lherapy sysLem ln glloblasLoma
mulLlforme
- 1993 (Aeblscher and kaLo) 1reaLmenL of amyoLrophlc laLeral sclerosls uslng
a gene Lherapy approach lnvolvlng lmplanLaLlon of geneLlcally englneered
mlcroencapsulaLed cells releaslng neuroLrophlc facLors
- 1998 (llre eL al) 8nA lnLerference demonsLraLed ln[ecLlon of double
sLranded 8nA shown Lo lnhlblL genes
istory and development
2000 to date
- 2003 a unlverslLy of Callfornla Los research Leam lnserLed genes lnLo Lhe
braln uslng llposome coaLed ln a polymer called polyeLhylene glycol
- Cene sllenclng may be a new way Lo LreaL PunLlngLons dlsease
- SclenLlsLs aL Lhe naLlonal lnsLlLuLe of PealLh (Maryland) have successfully
LreaLed meLasLaLlc melanoma ln Lwo paLlenLs uslng klller 1 cells
geneLlcally reLargeLed Lo aLLack Lhe cancer cells
- March 2006 successful use of gene Lherapy Lo LreaL Lwo adulL paLlenLs
for a dlsease affecLlng myelold cells (naLure Medlclne March 2006)
- May 2006 a Leam of sclenLlsLs led by ur Lulgl Maldlnl and ur 8rlan
8rown from Lhe San 8affaele 1eleLhon lnsLlLuLe for Cene 1herapy (PS8
1lCL1) ln Mllan lLaly uLlllzed a newly uncovered neLwork of genes
regulaLed by molecules known as mlcro8nAs
istory and development
- november 2006 9resLon nlx from Lhe unlverslLy of 9ennsylvanla School
of Medlclne reporLed on I8x496 a genebased lmmunoLherapy for Lhe
LreaLmenL of PlI LhaL uses a lenLlvlral vecLor for dellvery of an anLlsense
gene agalnsL Lhe PlI envelope
- May 2007 Moorfleld Lye PosplLal and unlverslLy of London announced
Lhe worlds flrsL gene Lherapy Lrlal for lnherlLed reLlnal dlsease 1he flrsL
operaLlon was carrled ouL on a 23 yearold 8rlLlsh male 8oberL !ohnson
- SepLember 2009 Lhe [ournal naLure reporLed LhaL researchers aL Lhe
unlverslLy of WashlngLon and unlverslLy of llorlda were able Lo uslng
gene Lherapy a hopeful precursor Lo a LreaLmenL for color bllndness
- november 2009 Lhe [ournal Sclence reporLed LhaL researchers succeeded
aL halLlng a faLal braln dlsease adrenoleukodysLrophy
- Aprll 2010 A paper by komromy et al deals wlLh gene Lherapy for a
form of achromaLopsla ln dogs