gene editing: swine in biomedical research (angelika schnieke)

8/20/2019 Gene Editing: Swine in Biomedical Research (Angelika Schnieke)

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Tegbm`sgbe Um`vers`tät Aómgbem

Keme Ed`t`mk

Im`aics `m f`haed`gic reseirgbWw`me

Imkec`ji Wgbm`eje




C`vesthgj F`htegbmhchky

7> yeirs hl kemet`g emk`meer`mk hl cirke imàics

9025-6>95

Frèl b`sthry? Aetbhds lhr kemet`g emk`meer`mk

Kemet`giccy ahd`lèd p`ks lhr f`haed`gic reseirgb

[by kemhae ed`t`mk





Wecegt`ve freed`mk hl pcimts imd im`aics

L`rst dhaest`git`hm 96>>> FG (dhk)

‐Ummituric' byfr`ds 7>>> yeirs ikh

(Auces? aice dhmjey imd i aire)

B`sthry hl kemet`g ahd`l`git`hm





902> Khrdhm, Vuddce 9st trimskem`g ahuse prhduged fy DMI a`grh`moegt`hm

9027 îca`ter, Fr`mster buaim KB trimskem`g ahuse

–Tbe àpc`g`t phss`f`c`ty `s th use tb`s

tegbmhchky th stàucite rip`d krhwtb

hl ghaaergìccy vicuifce imàics‑

Fectv`cce p`k (KB)

9025 îca`ter, Fr`mster ^rhdugt`hm hl trimskem`g

riff`ts, sbeep imd p`ks fy a`grh`moegt`hm.


9025-6>95





902< ^bira`mk

Ipprhved prhdugts

6>>< Imt` tbrhaf`m @@@

6>9> G9 esterise `mb`f`thr





^bira`mk? reghaf`mimt l`fr`mhkem- l`fr`m seicimt, bieahstit, imt`-idbes`ve

gbi`ms

77> jDi bexiaer

Auct`pce d`sucpb`des

L`fr`mhkem

Umtreited ghmtrhc

it 94 diys

extems`ve idbes`hms

L`fr`m @ treited

it 94 diys

mh idbes`hms

L`fr`m @

phcyaer

L`fr`m ahmhaer

`m ig`d`g fuller

Meutric`s`mk

fuller





Driwfigjs hl prhmugceir a`grh`moegt`hm

DMI a`grh`moegt`hm? hmcy 39-5% trimskem`g imàics

Trimsphshms? s`ze cà`tit`hm

\`ric vegthrs? silety ̀ ssues, s`ze cà`tit`hm

Mh ghmtrhc hver wbere tbe trimskeme `mtekrites

Trimskeme imicys`s hmcy phss`fce ilter f`rtb

Mh ghmtrhc hver sex hl lhumder - aices icchw lister lchgj expims`hm

Hmcy keme idd`t`hm phss`fce - mh keme decet`hm, ahd`l`git̀ hm, sufst`tut`hm





Wbeep zykhte

^`k zykhte ^`k zykhte ilter gemtr`lukit`hm

A`grh`moegt`hm? sbeep, p`k

@aikes? B. M`eaim, Air`emsee

Wbeep zykhte





DMI a`grh`moegt`hm? hmcy 39-5% trimskem`g imàics

Trimsphshms? s`ze cà`tit`hm

\`ric vegthrs? silety ̀ ssues, s`ze cà`tit`hm

Mh ghmtrhc hver wbere tbe trimskeme `mtekrites

Trimskeme imicys`s hmcy phss`fce ilter f`rtb

Mh ghmtrhc hver sex hl lhumder - aices icchw lister lchgj expims`hm

Hmcy keme idd`t`hm phss`fce - mh keme decet`hm, ahd`l`git`hm, sufst`tut`hm

Driwfigjs hl prhmugceir a`grh`moegt`hm





[bit dh we wimt8

[e wimt? 9>>% trimskem`g imàics

Imicys`s hl trimskem`g stitus felhre kemerit`hm hl imàics

Deg`de tbe sex hl imàics

Ghmtrhc hver wbere tbe trimskeme `mtekrites

Aetbhds lhr preg`se aim`pucit`hm hl tbe imàic kemhae

Bhahchkhus reghaf`mit`hm/keme tirket`mk

Gecc aedìted trimskemes`s




Tirketed keme ahd`l`git`hm

EW hr `^W geccs

Fcisthgyst

Tirket`mk \egthr Trimslegt`hm

Bhahchkhus reghaf`mit`hm

Wecegt`hm

Whait`g geccs

Gb`aer`g im`aics

Ahuse EW geccs (9029) C`vesthgj

EW geccs `^W geccs

^hrg`me `^W 88





Eafryh trimsler ^rekmimgy

(95> diys)

Gecc trimsler

Hhzyte

Emugceit`hm

Ecegtrh lus`hm

Eafryh gucture

Kemet`g aim`pucit`hm

DMI, VMI imicys`s

Whait`g gecc

Wciukbter bhuse

@m v`trh

@m v`vh

7VVeduge

Vel`me

Vepcige

Vepcige

Veduge

900< Dhccy

Vel`me

Tirketed keme ahd`l`git`hm

Mugceir trimsler





900< L`rst imàic gchmed lrha im iduct shait`g gecc (Dhccy)

900; L`rst gchmed trimskem`g ciaf (^hccy, Ahccy, Bhccy, Hccy)

9000 L`rst keme tirket`mk `m c`vesthgj (Dìmi imd Gup`d)

6>>> L`rst gchmed p`ks lrha im iduct shait`g gecc (A`ccè, Gbr`sti,

Icex`s, Girrec & Dhtgha)

B`sthry hl kemet`g ahd`l`git`hm






9025-6>95



[by kemhae ed`t`mk





Femgb th feds`de

Fis`g reseirgb

Estifc`sb`mk mew ahdecs

^rhhl hl pr`mg`pce

Trimscit`hm `mth tbe gc`m`g

Wuggess rite 9/5.>>>

Gc`m`gic trìcs

îtèmts

Cirke imàic ahdecs lhr f`haed`g`me

^regc`m`gic tests

\ic`dit`hm / Wilety

Wà`cir`ty ̀ m pbys`hchky/imithay





C`meir krhwtb `m c` le expegtimgy hver cist 9;> yeirs@mgreised c`le expegtimgy `mgreised gimger `mg`demge

Bicl tbe fif`es fhrm `m Oipim `m 6>>;

w`cc c`ve th fe 9>;





[by dh we meed cirke imàic gimger ahdecs8

Ahuse ahdecs

Umt`c regemtcy, kemet`giccy del`med ahdecs hmcy `m a`ge

Ahuse ahdecs dh mht icwiys repc`gite buaim d`seise pbemhtype

Cirke imàic ahdecs - p`k

Wà`cir s`ze th buaim

Use hl buaim s`zed equ`paemt (surkery, ridìt`hm treitaemt, àik`mk)

Chmker c`lespim tbim a`ge

Chmk`tud`mic studès `m s`mkce `md`v`duic

Wà`cir pbiraighj`met`gs

Gim fe led buaim dèt

D`seise pbemhtype gchser th buaims (8)




C`vesthgj F`htegbmhchkyMiture Vev`ews Gimger 2, 72;-702 (Aiy 6>>2)Lc`s`jhwsji et ic. 6>96: Kistrhemterhchky 947, 99;7-99;5

^hrg`me gimger ahdec? Ghchregtic gimger

Keme tirket`mk `m shait̀ g geccs, secegt`hm

Mugceir trimsler

ahuse ≮ buaim 1 p`k





Hrkim speg`l`g `mdug`fce hmghkem`g autit`hm hl p57

Keme tirket`mk `m shait`g geccs, secegt`hm

Mugceir trimsler

Airjer keme expressed

T^57V9<;B s`cemt*

chx-si-fs-phcyI-phcyI-phcyI-chxGre

reghaf`mise

Trimslegt`hm, secegt`hm

^rhahter Gre reghaf`mise

Mugceir trimsler

R

T^57V9<;B expressed*

chx

Hrtbhchkues

Buaim V9;5B

Ahuse V9;6B

^`k V9<;B

Ceugbs et ic., 6>96 imd C` et ic., 6>95





D`seise Kemet`g ahd`l`git`hm Veleremge

Gimger

\ir`hus gimgers

Fisic gecc girg`mhai

Freist gimger

–

Ghchregtic gimger

T^57

KC@6

v-B-VIW

FVGI9

I^G

Ghmd`t`hmiccy igt`vited tirketed autit`hm

Buaim trimskeme

AAT\ d`regted v-B-ris trimskeme

Jmhgjhut

Tirketed trumgit`mk autit`hms

Ceugbs 6>96

AgGicci-Airt`m 6>9>

Piaijiwi 9000

Cuh 6>99

Lc`s`jhwsji 6>96

Gird`hvisgucir d`seises

Itberhsgcerhs s̀Bypergbhcesterhceaì

M`tr`g hx`de rekucit`hm

Bydrhkem perhx`de rekucit`hm

Itberhsgcerhs s̀

Bypertr`kcyger`deaì

CDCV

^GWJ0

MHW7

Giticise

^ÎV-K

I^HG7

Jmhgjhut

Buaim autimt trimskeme

^hrg`me trimskeme

Buaim trimskeme

Jmhgjhut

Buaim trimskeme

Gircshm 6>96 Ic-Aisbbid` 6>97

Bih 6>><

[byte 6>99

Pimk 6>99

[e` 6>99

Dìfetes aecc`tus

Dìfetes type 6

^MDADìfetes type 7 (AHDP)

K@^V

@MWBML-9ι

Buaim dha`mimt mekit`ve autimt trimskeme

^hrg`me autimt trimskemeBuaim dha`mimt mekit`ve autimt trimskeme

Vemmer 6>9>

Vemmer 6>97Uaeyiai 6>>0

Meurhdekemerit`ve d`seises

Iczbeàer‐s d`seise

Bumt`mkthm‐s d`seise

Wp`mic ausgucir itrhpby

I^^

BTT

WAM9

Buaim autimt I^^ trimskeme

Buaim autimt trimskemes

Jmhgjhut

Tijeugb` 6>>>

Fixi 6>97

Chrshm 6>99

Hpbtbica`g meurhdekemerit`ve d`seises

Vet`m`t`s p`kaemthsiWtirkirdt d`seise-7

VBHECH\C4

^hrg`me imd buaim autimt trimskemesBuaim autimt trimskemes

Vhss 6>96Whaaer 6>99

Htber d`seises

Gyst`g l`frhs`s

Dugbemme ausgucir dystrhpby

Bieahpb`cì I

WG@D

GLTV

DAD

L2

@C6VK

Jmhgjhut

Jmhgjhut

Jmhgjhut

Jmhgjhut

Vhkers 6>>2

Jcyaùj 6>97

Jisb`wijuri 6>97

Wuzuj` 6>96






9025-6>95



[by kemhae ed`t`mk





VHWI 6<

VIK9

@C6Vη

KKTI9

CDCVDAD

^57

I^G

JVIW

GLTV

FVGI9

WAM9

@k beivy gbi`m

@k c`kbt gbi`m

VHWI 6<

VIK9

@C6Vη

KKTI9

CDCVDAD

^57

I^G

JVIW

GLTV

FVGI9

WAM9

@k beivy gbi`m

@k c`kbt gbi`m

Keme tirket`mk `s `mell`gèmt requ`res guctured geccs

Keme tirket`mk `m shait`g geccs `s very `mell`gèmt~9>>x cess ell`gèmt tbim `m ahuse EW geccs

Lew kemes tirketed `m sw`me `m tbe cist 95 yeirs

\ery lew exiapces hl ghmd`t`hmic keme tirket`mk

Ghapcex aim`pucit`hm very, very `mell`gèmt

Tirketed ahd`l`git`hm hmcy hm 9 iccece freed`mk th bhahzykhs`ty

[by kemhae ed`t `mk

9 6 47

6WI fsr 7*

Chx Chx





Keme ed`t`mk `s very ell`gèmt (=4>%)

Ed`t`mk fhtb icceces

Auct`pce tirket kemes sàuctimehuscy

Gim fe dhme `m geccs hr eafryh

Megessiry vegthrs ire eisy th ghmstrugt Ippcèd is DMI, VMI, prhte`m

[by kemhae ed`t `mk

9 6 47

6WI fsr 7*

*Chx Chx

L`k. Miture ^rhthghcs 0, 29>‗26; (6>94)





Keme ed`t`mk `s very ell`g`emt




Megessiry vegthrs ire eisy th ghmstrugt

Ippc`ed is DMI, VMI, prhte`m

[by kemhae ed`t `mk


Keme ed`t`mk

Imicys`s hl s`mkce gecc gchmesDMI, VMI, ^rhte`m

Mugceir

trimsler

^`kcet w`tb pred`gted

ahd`l`git`hm

Imiciys`s phst pirtua

Ahd`l`git`hm8

Ahsi`g`sa8

Keme ed`t`mk





Keme ed`t`mk? exiapce xemhtrimspcimtit`hm

Kemhae-w`de `migt`vit`hm hl phrg`me emdhkemhus retrhv`ruses (ÊV\s).

Pimk et ic., Wgèmge. 6>95 Mhv 6;:75>(<6<4)?99>9-4.

<6 ÊV\s





Keme ed`t`mk `s very ell`gèmt




Gim fe dhme `m icc spegès (mh requ`reaemt lhr EW gecc hr WGMT)

Megessiry vegthrs ire eisy th ghmstrugt

Ippcèd is DMI, VMI, prhte`m

[by kemhae ed`t `mk






Buaim phcygchmic imt`fhdès- ahre ellegt`ve tbim aIfs lhr piss`ve àaumhtberipy

- aà`g mituric àaume resphmse

Gim hmcy fe prhduged `m pehpce hr trimskem`g imàics

Vequ`re imàics cirker tbim a`ge lhr prhdugt`hm hl idequite quimt`tès hl serua.

Buaim phcygchmic imt`fhdès

prhduged `m riff`t

Viff`t mugceir trimsler? d`ll`guct

_ijbirtgbemjh et ic., 6>99 F`hc Veprhd 24

ûtit`ve riff`t EW geccs





@aaumhkchfuc`m keme d`srupt`hm us`mk _`mg L`mker Mugceises6>99 Lc`s`jhwsji et ic ^ChW HME <(<)? e69>45

_LM VMI

_LM VMI

+ tirket`mk vegthr DMI

prhmugceus & gythpcisa

Tirketed repcigeaemt `mup th 92% hl letuses.





^hrg`me gimger ahdecs

JVIW, T^57, I^G `mvhcved `m aimy d`lleremt types hl gimger

JVIW? pimgreis, cirke/saicc `mtest`me, cumk, test`s, c`ver, tbyrh`d

T^57? ahst buaim tuahurs, saicc gecc cumk girg`mhai

I^G? Ghchregtic gimger, kistr`g imd duhdemic aic`kmimg`es, pimgreis, f`c`iry trigt,

kicc fcidder, bepithfcisthais

Oust idd Gre

@m v`vh GV@W^V/Gis0 ippc `git`hm

Oust idd 9 hr ahre ku`de VMIs





^bira`mk

Vekemerit`ve

Aed`g`m

D`seiseahdecs

Kemet`giccy ahd`l `ed

cirke im`aics

@aprhv`mk Beictb

^ r h d u g t s

E m v ` r h m a e m t





Kemhae ed`t`mk `m sw`meFeyhmd f`haed`g`me

Kemhae ed`t`mk `m sw`meFeyhmd f`haed`g`me

Ed`ted kemes Tirketed kemes

A`grh p`ks is pets92 | MITUVE | \HC 56< | 9 HGTHFEV 6>95

TICEMs ̀ migt`vited 9 hl 6 ghp`es hl tbe krhwtb bhrahme regepthr keme (KBV)

‒Dhufce-ausgced‐ p`ksMiture 567, 97‗94 (>6 Oucy 6>95)

Autit`hm `m tbe ayhstit`m keme (AWTM).

L`kbt`mk Ilr`gim Ww`me Lever

–^`k 6<‑ Vhsc`m @mst.

Wecegt`ve trimsler hl mituriccy hggurr`mk keme vir`imts

Ictermit`ve aetbhd th freed`mk





Kemet`g emk`meer`mk

Kemhae emk`meer`mk / Kemhae ed`t`mk

Icchws preg`se exgbimke hl s`mkce hr auct`pce fise pi`rs `m tbe kemhae

^rerequ`s`te? kemhae sequemge

Ghmtrhc? kemhae sequemg`mk

Aiaaic`im Kemhae

7.7 x 9>0 fp





Kemet`g ahd`l`git`hm? Gis0-fised ippc`git`hms

Wimder & Ohumk, Miture F`htegb Ipr`c 94




Kemet`g emk`meer`mk hl cirke im`aicsWtite hl tbe irt

GV@W^V/Gis0

Ceid`mk thhc `m tbe l`ecds hl symtbet`g f`hchky imd kemhae emk`meer`mk.





GHWT Igt`hm FA97>2

Wbir`mk Idvimges hm Cirke Im`aic Ahdecs

bttp?//www.siciia.kemzemtrua.cau.de/





Tegbmhchkès lhr kemet`g aim`pucit`hms ire ivi`cifce imd ghmt`mue th

àprhve

@m `tsecl mht i sull`gèmt reishm th prhduge kemet`giccy ahd`lèd cirkeimàics

Lhr eigb prhoegt r`sj imd femel`ts bive th fe evicuited

Imàic weccfe`mk bis th bive i b`kb pr`hr`ty

@l `t prhv`des imd idvimtike lhr tbe emv`rhmaemt, tbe beictb hr weccfe`mk hl

buaim hr imàic, tbim kemet`g ahd`l`git`hm (`mgc. keme ed`t`mk) `s i

phwerluc imd preg`se thhc.

Lew cifhrithrès bive gipig`ty th girry hut cirke imàic experàemts

Tàe imd ghst `mtems`ve meed th ghhrd`mite ellhrts

Etb`gic imd pufc`g ghmgerms meed th fe iddressed

Kemet`g emk`meer`mk hl cirke imàics





Imàic ahdecs

[hrj w`tb imàics `s str`gtcy rekucited

Imàic experàemts requ`re ipprhvic fy khvermaemtic fhdy

F`haed`g`me

Gc`m`gic imd rekucithry meed lhr devechpaemt hl cirke imàic ahdecs

\ir`hus ahdecs hl buaim d`seises ire fe`mk devechped

Kemhae ed`t`mk? hme ahre thhc `m tbe kemet`g thhcfhx Veduge, Vel`me Ikr`gucture

I thhc th àprhve imàic beictb (d`seise res`stimge/prhtegt`hm), tri`ts

Veduge emv`rhmaemtic àpigt

Vepc`gite mituric virìmts (mht trimskem`g) kemet`giccy ahd`lèd 8

kemet`giccy àprhved 8

cifecc`mk 8

Kemet`g emk`meer`mk hl cirke imàics





TUA Jc`m`jua regbts der @sir Dèter Wiur

Kómter Wgbme`der

Wtelim Eser

Vhcimd Wgba`d

Jcius-êter Oimssem

CAU

Firfiri Jesscer

Aiyujh Jurhae

\icer` _ijbirtgbemjh

Egjbird [hcl

Bimmhver

Foürm êtersem

Be`mer Mèaimm

Vicl Wgbw`mzer

Vhgbe

Ohsel ^citzer

Imthm`h @kces`sis

Ucr`gb Gerti

TUA [_[Femed`jt Fiuaer

Airceme Edc`mker

Dimèci Leccmer

Jhmrid L`sgber

Titìmi Lc`s`jhwsji

Jrzyszthl Lc`s`jhwsj` Iceximder J`md

Wàhme Jrimer

Wbum C`

Dem`se Mkuyem

Feite Vèfc`mker

Imoi Wiiclrimj

Er`gi Wgbucz

Girhc`m [imder

Becabhcz

Vicl Jóbm

[hclkimk [urst

^hzmim Um`vers`ty hl C`le Wgèmges

Airej Ww`thmsj ,̀






Tbimj yhu lhr yhur ittemt`hm

gene editing: swine in biomedical research (angelika schnieke)

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