KHOfl HOC - C 6 N G N G H ^ V A B 6 | Mdi
SAN XUAT PROniH TAI TO HQP TAI VIET HAM
N 1 - | 0 N C 5 KMOl D A U T I E M N A N G
QUAN QU6C O A N G , TRAN H O A N G I Tmbnq Ba\ hpc Nguyen T3t
lpc fhoa hpc Tl/ rihi«n, Dai hpc
Ngdy nay, vifc nghiSn clJu sin xud't vd (Jng dgng protein tdi ttf h^p trSn th^^gldi da pliat tritfn khd m^nh me, d^c bift l i trong cdc ITnh v^fc y dUtfc, sinh hpc, nOng nghifp... 061 vdi Vift Nam, mfc du vd'n 6i ndy mdi dirpc bit diu ndm 1999 nhifng da dpt dirpc nhilu l(e't qud ddng l(h[ch if. Cd thtf ndi ddy id hirdc l(hdi dtfu titfm ndng cho vifc nghien ci}u vd sdn xud't protein tdi ttf hpp trong thdi gian tdi phpc vg nhu clu trong nirdc va titfn tdi xud't l(htfu.
od MINH si
Vng dung ciia protein tai to hpp
Protein tai to hop la cau true dUdc djch ma tU cac phdn til DNA tdi to hop - dU0c tgo ra tQ cac phdng thi nghiem bdng cdch tgo ddng phdn tCf nham ghdp cac nguon vat c h i t di truyin tU cac ca the khac nhau, tgo ndn mdt cau true khdng the tim thd'y trong bat ky cd the sinh vdt ty nhidn nao. Qud trinh l i p ghdp
c l u true di truyin hodn todn cd the thuc hien dUdc bdi vi c l u true cua chung la hodn toan gid'ng nhau, chf khac 6 vi trf cac nucleotit. DNA ngogi lai dQ0c dua vao vd lidn k i t vdi vdt chd't di truyen cGa t l bdo chu, sau dd Chung dupc nhdn Idn cung vdi qud trinh nhdn ddi cua te bao md chung xdm nhdp [6].
Ngay nay, protein tdi td h0p va cdc sdn p h i m thu nhdn dU0c
A. Khang the chuot (100% la tir chupt)
Hinh 1 cdng ngh^ Protein t^i t6 h0p t^o nSn nhOng cSu trOc, khiing thS dan ddng
thdng qua ky thuat DNA tdi to hqp cd mdt trdn thj trudng dudi nhilu dang rat khac nhau, chung duqc siS dyng nhU Id sdn pham t h i l t yeu trong cac nha thudc tdy y, phdng mgch bac sT, phdng thi nghidm sinh y hpc ldm sdng. Xa hdn nQa, cdc sdn p h i m hay sinh vdt duqc tgo ra tU ky thudt DNA tdi td hqp cd rd't nhilu trong cdc ndng trgi, sidu thj hay cdc cQa hang thu nudi Idm cdnh trong gia dinh [5].
Ngodi ra, protein tai to hqp cung duqc Ung dyng nhilu trong y hqc ngUdi vd ddng vdt, trong trdng trpt, ky thudt sdn xud't sinh hqc nhU: insulin tdi to hqp, hormon tdng trudng tai t6 hqp (HGH, somatotropin), yeu td ddng mdu tdi t l hqp VIII, vac- xin ngUa viem gan sidu vi B tai t l hqp, c h i n dodn nhiem HIV, ggo hat vdng (mdt logi protein tdi to hqp duqc sdn xuat thdng qua su b i l u hidn cDa cac enzym ddp Ung vdi qua trinh t i n g hqp p-carotene), cdy trong khdng
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KHOfl HQC - CONG N G H $ Vfl TOI M(3l
thud'c diet cd, cdy trdng khang sdu benh...
Qng dung rdng rai vd nhilu nhat cua protein tdi td hqp la trong nghien cUu cd bdn thudc ITnh vUc sinh hoc vd y sinh [2].
Protein tai to hqp dUdc sCf dyng de dmh dgng, dd tim vd xac djnh trinh tu gen, thdng qua dd tim hilu chUc ndng ciia gen ndo dd.
Cdc d i u dd protein tai t l hqp duqc sCr dyng trong cdc phdn tich bieu hidn gen trong t l bao rieng biet, md hay toan bd cd t h i sinh vdt. Protein tdi to hqp duqc sCf dyng rdng rdi nhU Id thudc thCt trong cdc thi nghidm trong phdng thf nghiem vd tgo ra cac thiet bi thdm dd khdng the de kiem tra tdng hqp protein trong t l bdo vd cdc sinh vdt [5].
Thi tnrong protein tai to hop hien nay
Hien nay thj trudng protein tai to hdp chUa phdt trien h i t tiem nang. Tuy vdy, dudi sU hd trd cung nhu ung hd cua cdc cdng ty dUdc phim Idn tren the gidi, nhat Id trong cdc ITnh vUc lieu phdp chuTa tn cho cdc benh thieu mdu, t i l u dudng, ung thU, viem khdp vd bdng, gid trj cua protein tai td hqp da dat con sd hdn 531?
USD vao ndm 2010.
Giufa nhj3ng nam 2001 va 2003, gid trj thj trudng cCia cdc proterin tdi to hqp tn lieu da tang tu 21,7 tT len den 31,7 tl USD.
Cac cdng ty cung cd'p dUpc phim Idn tang tU 6 ldn d i n 12 cdng ty vd chilm thj trudng tdng cdng tU 52% len tdi 64%. TU nam 2004 den 2010, gia trj cua chung da tang tU 35,8 t? len den 53 t? USD.
Trong giai dogn nay, cdc cdng ty cung cd'p dUdc phim Idn trdn thigidi chilm tong cdng 58% thj trudng.
Trong ITnh vUc trj lidu huylt
hqc, sau khi cdc cdng ty ldn nhu Amgen's Epogen/Aranesp va Johnson & Johnson Procrit/
Eprex nhupng Igi quyin thUdng mgi, gid tri thj trudng cCia cdc protein tdi t l hqp trong ITnh vyc ndy vdn dUng d i u trong tidu thy vd phdn phd'i, tong sdn luqng tieu thy cua chung dgt 15,9 tf USD trong ndm 2010, chilm 1/3 thj trudng cCia cdc protein tdi t l hqp dung trong trj ligu. Tuy nhidn, trong ITnh vyc trj lieu vidm khdp, bdng vd rdi logn midn djch, dupc ho trq nghien ciiu vd phat trien bdi Amgen's Enbriel, chf tang hdn gd'p ddi, tU 2,5 tf ndm 2004 ien d i n 5,2 tf USD trong ndm 2010.
Cdc protein tdi t l hdp dang erythropoietin dan dau thj trudng vdi doanh sd ban hdng Id hdn 11,4 ty USD trong nam 2010, chilm hdn 1/5 gia tri thi trudng.
Theo sau Id interferon, chiem thi phan 19% trong nam 2010 vdl doanh s i bdn hdng 10 ty USD.
Cdc protein tdi to hpp cd su phat triln mdt each chdng mat, vdi doanh sd ban hdng gap gan ba lan tu ndm 2004 d i n nam 2010 (6,1 ty USD), thj phan tang ga'p ddi, tu 6% d i n 12% trong ndm 2010.
Qua trinh nghien^niu va san xuat protein tai to hop d Viet Nam
6 nUdc ta, vide nghien cUu protein tdi t l hqp mdi dUde chinh thUc b i t dIu tu 1999 vdi dy dn
"Nghidn cUu sdn xudt amylase (mpt enzyme trong nUdc bqt Idm xuc tdc sU phan huy tinh bdt thdnh dudng) tdi to hqp" do TrUdng Nam Hdi vd cdc edng sU (Vidn Cdng nghd sinh hoc, Vidn KHiSiCN Vidt Nam) thUc hidn.
Nghidn eUu nay la budc dot phd dau tidn vd la d i l u kidn tien quylt cho cdc nghidn cufu hodn ehlnh
sau ndy. K i t qud eua nghidn cUu ndy cho thiy, vai trd quan trpng cua cdc protein tdi t l hpp trong sdn xud't lUPng thyc thyc phim [10].
Ndm 2003, T r i n Linh Thudc vd cdc edng sy (TrUdng Dgi hpc Khoa hpc TU nhidn, Dgl hpc Qudc gia Tp Hd Chi Minh) dd thyc hidn dy dn "So sanh hd thd'ng bilu hidn gen trong eac t l bdo cOa vi khuIn E. coli (vi khuIn pho biln nhat duqc sijf dyng tren todn t h i gidi nhu mdt t l bdo trung gian d l sdn xuit cdc protein tai to hpp". DU dn da de xud't cac quy tac lUa chpn hd thd'ng vector phu hdp vdi myc tidu sdn xuat protein va cac giai dogn trong qud trinh len men, sau khi Idn men. K i t qud cua dU an cung cap cd sd cho nghien cUu cdng nghe sdn xua't va tinh c h l protein tdi t l hdp, nhim phyc vu eho nhu cau chan dodn va phdng ngUa bdnh 6 ngudi, ddng vat va thuc vat [8].
Giai dogn 2006-2009, TrUdng Nam Hai va eac dong nghiep da thUe hien dU dn "Nghien eUu sdn xud't vac-xin phdng chdng cum gia cam A/H5N1 bang chOng vi khuan tdi to hpp 6 Viet Nam".
Sy thdnh cdng cua dy dn ndy da md ra mdt k^ nguydn mdi trong cudc chien chdng dich cum gia e l m dang lan rdng tren todn t h i gidi ndi chung vd Viet Nam ndi ridng. Vdi vide sQ dyng cdc lodi vi khuIn bdn dja, phUdng phdp phdng ngUa vd dieu trj dgc hidu cho thay hidu qud hdn han trong qua trinh ngdn chgn viec phat tan va Idy lan benh eua virus cum gia e l m .
CQng trong thdi gian nay, T r i n Linh Thudc vd Hoang Van Qud'c ChUdng da hoan thanh du dn "Nghien cUu sdn xuat insulin tai to hpp". Ddy Id mdt du dn
So,h4„g5 2 0 i 2 K H " o A H o ' c 2 '
KHOfl HQC - CONG NGH^ VA B6\ M6I
cd y nghTa ldn ddi vdi Vidt Nam khi ma chf trong 10 ndm 1990- 2000 ty Id benh tieu dudng d cdc thdnh phd' idn tdng tU 2 dd'n 4%.
Sd ngudi m i c bdnh t i l u dudng Id khodng 4,5 tridu ngUdi, chilm 5,7% ddn sd. Theo Udc tfnh thi nhu c l u insulin d Vidt Nam Id r l t eao, trong khi td't cd cdc ngudn sLf dyng insulin eho b§nh nhdn m l c bdnh t i l u dudng d i u phdi nhdp khiu tU nude ngodi, khdng eh? tdn kdm ngogi td, khdng chCi ddng dupe ngudn thud'c md cdn khdng ddp Ung dupc cho cdc bdnh nhdn d l d i l u trj kjp thdi.
De ddm bdo d i l u trj eho bdnh nhdn vdi lilu hdng ngdy tU 0,5 d i n 1,0 U/kg trpng luqng cq t h i , Vidt Nam can nhdp k h i u khodng 120-240 trieu U/ndm, tUdng duqng 420-840 kg/ndm (insulin 100U = 3,5 mg). Sy thdnh cdng cija Du dn nay da md ra hy vpng eho khd nang sdn xud't insulin tai to hdp tai Vidt Nam trong nhUng nam tdi [9].
Nam 2009, Le Tram NghTa Thu va cpng sij (Phdng Thf nghiem te bao gdc thudc TrUdng Dgi hpc Khoa hpc Ty nhien, Dgi hpc Qudc gia Tp Hd Chf Minh) dd thdnh edng trong qua trinh tao ra cdc ddng te bdo CHO- K1 on dinh {Chinese Hamster Ovary) cd chijra gen tPA {tissue Plasminogen Activator) - Id mdt yeu td rd't quan trpng cd dnh hudng tryc t i i p len qud trinh kfch hogt phdn gidi cyc mdu ddng trong cd t h i ddng vdt, Idm gidm nguy cP eua eac trieu chUng nhu xd vUa ddng mach, nhdi mdu cd tim hoac ddt quy... PhUdng phdp nay da tgo duqc ddng t l bdo CH0-K1 ed t h i sdn xuit 0,9 den 1,6 pg fPA/ngdy [3].
Nam 2010, Le T r i m NghTa Thu va Dd Minh ST t i l p tyc thCf nghiem sdn xud't Erythropoietin {EPQ tdi td hqp thdng qua
chuyin gen trdn t l bdo CHO- K1. Cdc nghidn cilu da cho thd'y k i t qud rd't tfch eye khi tgo ra ddng t l bdo cd khd ndng sdn xuit EPO dd duqc djnh lupng thdng qua phUdng phdp ELISA sandwich Id 2,055 ± 0,015 p g / t l bdo/ngdy [4].
Cung trong ndm 2010, Quy Phdt triln KH&CN qudc gia da h6 trq D 6 Minh ST vd cdc ddng nghidp dU dn "Tgo khdng t h i ddn ddng tdi t l hqp IgG ed t h i nhdn dgng vd ngdn chdn thy t h i EGF sCf dyng trong c h i n dodn vd d i l u trj ung thu d ngudi bing phUdng phdp chuyin gen trdn td bdo ddng vdt". Du dn da mang Igi hy vpng trong sdn xuit dupc phim quan trpng d l c h i n dodn vd dilu tri ung thu, cdn bdnh nguy hiem nhit tgi Vidt Nam [1], [7].
Ket luan
Mac du Viet Nam la mdt nUdc dang phdt trien, xuat phdt d i l m v l KH&CN thd'p, nhung ede nghidn cUu ve protein tdi t l hqp d Vidt Nam dUpc phat triln ngdy cdng mgnh me. TU cac nghidn cUu vd sdn xuat Ung dyng cdc logi protein thyc phim, ch^ng hgn nhu amylase hodc protein d i l u trj d ngUdi nhU insulin ddn cdc nghien cCfu v l cdc protein tdi t l hpp dung trong y hpc vd rd't ed gid trj trdn thj trudng nhU tPA, erythropoietin hodc IgG tai t l hpp. PhUPng phdp nghidn cUu ngdy cdng chfnh xdc vd hieu qud hdn cung vdi chi phf nghidn cUu sdn xud't tdng cao, do thay doi t l bdo chuyen gen \(s vi khuan pho biln sang t l bao ddng vdt.
Cd the ndi ddy Id nhOng nd li;c khdng ngi/ng cCia ede nhd khoa hpc Viet Nam trong ITnh vi/c cdng nghe sinh hpc. Day la nhijfng khdi d i u tiem ndng de Viet Nam chiing ta tiep tyc vOng budc trdn
con dudng phdt trien cdng nghd sinh hpc ndi chung va sdn xuit protein tdi \6 hqp ndi ndng nhim phdt triln cdc sdn phim phyc vy nhu c l u trong nudc vd tiin tdi sdn xudt cdc sdn phim xuit k h i u sang cdc nudc khdc •
Tai lidu tham khao
I Ob Minh ST, Quan Outic Ddng vA c^ng SI/. T^o khdng th4 (Son ddng lii iS hpp IgG c5 th4 nh$n d9ng v& ngSn ch$n thv the EGF s^
di^ng trong chin doAn vd diiu tn ung thu i ngudi bAng phUOng ph&p chuyin gen lr6n ti bdo ddng v$t. Dv An Nalosted 2010-2012
2. Johnson I S (1983). 'Human insulin from recombinant DNA tflchnology*. Science 219 (4585)'632-637.
3. L6 T r i m NgtiTa T h j vd cljng si;, T$o ddng 6n djnh ti bio CHO-K1 (Chinese Hamster Ovary) chUa gen ting hop sin xuit tPA (tissue Plasminogen Activator). Tap chl Khoa hpc C6ng nghi$p 2010. D^i hoc COng nghi$p TpHCM. Sfi 4. 52-57.
4 Lfi Trfim NghTa ThU, Db Mmh ST va cOng SI/ Sin xuit Erythropoietin thdng qua chuyin gen udn ti bAo CHO - Kl (Chinese Hamster Ovary Cell Type Kl) Tap chi Khoa hpc va Phdt Iri^n 2010. D91 hpc Ndng nghiep Ha N$i: Volume 8, No. 3 498-504
5.Lear J. (1978) Recombinant DNA' TTie Untold story. New York: Crown Publishers, p, 43.
6 Peter Walter, Alberts, Bruce, Johnson, Alexander S., Lewis, Julian, Raft, Martin C , Roberts. Keith (2008). Molecular Biology of the Cell (5th edition. Extended version). New York:
Garland Science. ISBN 0-8153-4111-3.
7. Quan Quoc Dang et al. Transient transfection of CH0-K1 cells in serum- containing medium and serum-free medium with gene coding for human IgG heavy chain protein. Journal of Sciences and Development 2010 (English issue 2), Hanoi University of Agriculture: 185-192.
8 TrSn Linh Thi/dc v ^ c^ng si/. Nghiin cOu hd thing biiu hidn gen trdn E.coIi nhim sin xuit protein lii ti hop. Dy An Bfi KH&CN, 2003-2004
9, TrUdng Nam H i i vS cfing sU- Sin xuSt vic-xin cum gia cim A/H5N1 t^ng cAc chung til ti hop ldi Vidt Nam. D i / dn Bfi KH&CN, 2006-2009.
10, Tritdng Nam HSi vd c^ng s^J Nghidn cOu sin xuit cAc protein tai ti hop c6 giA tri tmng y duoc phim. D y a n Bfi KH&CN. 2003- 2004.
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