Prisys Biotech, tsim nyob rau hauv 2011, yog CRO tshwj xeeb hauvnon-tus qauv kab mob tib neeg primate (NHP).. Peb muab kev daws teeb meem raupharmacology thiab kev tshawb fawb txog kev ua tau zoo, kev ntsuam xyuas kev nyab xeeb, kev tshawb fawb biomarker, thiab kev siv lub tswv yim siv tau. Siv peb cov qauv tsiaj tshwj xeeb, suav nrog NHPs, cov dev sim, peb muab cov txiaj ntsig zoo thiab kev kwv yees uas ua rau muaj txiaj ntsig zoo rau kev txhais lus ntawm kev tshawb fawb biomedical, txo qhov kev pheej hmoo ntawm kev siv tshuaj tsis ua haujlwm.
Cov ntshav-brain barrier (BBB) yog ib qho teeb meem loj tiv thaiv cov tshuaj nkag mus rau hauvCentral paj hlwb (CNS)los ntawm periphery. Raws li feem ntau ntawm lub paj hlwb capillaries, BBB tswj cov ion tshuav nyiaj li cas thiab kev thauj mus los ntawm cov khoom noj thaum ua raws li kev txwv tsis pub muaj cov khoom tsis zoo. Cov capillaries no yog tsim los ntawm lub hlwb microvascular endothelial hlwb, ncig los ntawm pericytes thiab ib tug 30-40nm tuab basal lamina, thiab them los ntawm astrocytic kawg-taw nyob ze neurons.
Txawm hais tias BBB nthuav qhia ntau cov proteins thiab receptors, cov txheej txheem no feem ntau yog tsim los rau kev thauj mus los. Dej- cov tshuaj soluble tuaj yeem nkag mus rau hauv txoj hauv kev paracellular, thaum lipid- cov tshuaj soluble tuaj yeem ua rau muaj kev cuam tshuam los yog nquag thauj los ntawm kev thauj cov protein. Ib txoj hauv kev tseem ceeb rau kev hla BBB yog receptor-mediated transcytosis (RMT), qhov twg cov tshuaj endogenous xws li hlau / transferrin, insulin, thiab lipoproteins nkag mus rau hauv lub hlwb. Txawm li cas los xij, feem ntau cov molecules me me thiab ze li ntawm tag nrho cov molecules loj feem ntau tawm tsam hla BBB vim yog cov junctions nruj thiab ABC transporter proteins.
Transferrin Receptor (TfR)
Transferrin receptor muaj ob hom subtypes: TfR1 thiab TfR2. TfR1 yog xaiv tau zoo heev hauv lub hlwb capillary endothelial hlwb thiab pab txhawb kev hloov pauv (Tf) endocytosis thiab transcytosis. Paub tias CD71, TfR1 yog hom II transmembrane glycoprotein tsim los ntawm ob 90 kDa subunits txuas nrog disulfide bonds. TfR2 kuj khi circulating Tf, tab sis nws lub luag hauj lwm physiological yog tswj cov qib hlau es tsis yog cellular hlau uptake. Ligands rau TfR, kev xa khoom xws li liposomes lossis nanoparticles, thiab receptor{10}}cov tshuaj tiv thaiv tshwj xeeb tuaj yeem hla BBB ntawm txoj hauv kev no.
Piv txwv li, radiolabeled EGF-conjugated anti-rat transferrin antibodies tau siv rau kev kuaj mob hlwb. Kev tshawb fawb ntawm bispecific antibodies tsom TfR thiab BACE1 (-secretase-1) rau Alzheimer's kab mob pom tias muaj kev sib raug zoo dua rau TfR ua rau ntau TfR nkag mus rau lysosomes thiab raug degraded. Yog li ntawd, qhov zoo tshaj plaws TfR affinity yog qhov tseem ceeb rau kev xa cov tshuaj tiv thaiv kab mob mus rau lub hlwb, ua rau kom pom qhov chaw ntawm lub hom phiaj.
Insulin Receptor (IR)
Ntxiv nrog rau qhov qhia tau zoo hauv daim siab thiab cov hnyuv, cov tshuaj insulin kuj tseem muaj nyob hauv BBB, ua txoj hauv kev tseem ceeb rau insulin nkag mus rau lub hlwb. Ib yam li ntawd, lwm yam tshuaj lossis cov tshuaj molecules tuaj yeem nkag mus rau hauv lub hlwb ntawm cov receptor no, yog tias lawv tuaj yeem khi rau nws.
Piv txwv li, radiolabeled peptide A 1-40 conjugated nrog insulin receptor antibody nce lub hlwb peptide concentration hauv rhesus liab piv rau cov tshuaj tiv thaiv tsis sib haum. Tsis tas li ntawd, lub hlwb - muab tau los ntawm neurotrophic factor (BDNF) conjugated nrog ib qho tshuaj insulin receptor antibody pom tias muaj ntau lub hlwb nyob rau hauv rhesus liab. Txoj kev no tau ua tiav tiav -L-iduronidase mus rau lub hlwb rau kev kho mob mucopolysaccharidosis, lysosomal cia teeb meem.
Tsawg-Density Lipoprotein Receptor (LDLR)
LDLR, cov protein ntau ntau, yog qhia hauv hlwb capillaries. LDL lossis lwm yam lipoproteins uas muaj ApoB100 lossis ApoE tuaj yeem khi rau LDLR, ua kom cov cellular uptake ntawm lipids. Cov txheej txheem no, hu ua LDL receptor pathway, tso cai rau cov molecules loj thauj mus rau hauv lub hlwb endothelial hlwb.
Cov kev tshawb fawb tsis ntev los no tau pom tias cov roj cholesterol-conjugated siRNA lub hom phiaj OAT3 mRNA, embedded nyob rau hauv endogenous lipoproteins, ua tiav xa siRNA mus rau lub hlwb nyob rau hauv nas, muab ib tug tej zaum gene silencing mus kom ze rau cov kab mob hlwb.
Tsawg-Density Lipoprotein Receptor-Related Protein 1 (LRP1)
LRP1, zoo ib yam hauv cov qauv thiab kev ua haujlwm rau LDLR, thauj cov ligands hla BBB, suav nrog A protein, cov ntaub so ntswg plasminogen activator, Apo-E2, thiab Apo-E3. LRP1 mediates Ib qho protein efflux los ntawm lub hlwb, ua rau nws lub hom phiaj rau kev kho mob neurodegenerative.
Leptin Receptor (LepR)
Leptin, peptide hormone tsim los ntawm 167 amino acids, tswj lub cev qhov hnyav los ntawm kev khi rau leptin receptors hauv arcuate nucleus thiab hla BBB ntawm transcytosis. Kev puas tsuaj lossis poob ntawm leptin receptors tuaj yeem ua rau rog rog. Cov kws tshawb fawb tau ua tiav xa cov nanoparticles conjugated nrog qhov tseem ceeb leptin sequence amino acids rau lub hlwb hauv nas.
Receptor rau Advanced Glycation Endproducts (RAGE)
RAGE, 35 kDa immunoglobulin superfamily transmembrane receptor, tau nthuav dav hauv ntau lub hlwb, suav nrog cov hlwb endothelial, cov leeg nqaij du, thiab cov neurons. RAGE cuam tshuam nrog A protein, kho nws txoj kev thauj mus los thoob plaws BBB. Tsis zoo li LRP1, uas pab txhawb A protein efflux, RAGE thauj A los ntawm lub periphery mus rau hauv lub hlwb.
Scavenger Receptor (SR)
Pom nyob rau hauv macrophages, SR kho qhov nce thiab txo qis ntawm LDL hloov kho. SR yog qhia nyob rau hauv lub hlwb microvascular endothelial hlwb, pab txhawb kev nqus ntawm polyanions zoo li succinylated proteins. SR I thiab II tau qhia nyob rau hauv lub hlwb microvessels, nrog SR I mediating vitamin E uptake hauv npua.
Xaus
BBB tiv thaiv lub hlwb los ntawm kev tiv thaiv cov khoom tsis zoo los ntawm kev nkag mus, thaum tso cai rau cov as-ham tseem ceeb dhau mus. Receptor-mediated transcytosis muaj txoj hauv kev rau biologics nkag mus rau lub hlwb. Los ntawm conjugating cuam tshuam receptors xws li transferrin lossis tsim receptor-cov tshuaj tiv thaiv tshwj xeeb thiab peptides, cov kws tshawb fawb tuaj yeem siv txoj hauv kev no rau kev xa tshuaj. Thaum TfR thiab IR yog cov kws tshawb fawb tshaj plaws rau CNS kev xa tshuaj, lwm cov receptors xws li LRP1, LRP2, LepR, RAGE, thiab SR kuj tuav lub peev xwm, txawm tias muaj kev sib tw ntau dua.
Tsim cov tshuaj rauCov kab mob CNStseem nyuaj, nrog rau ob peb qhov kev sib tw hauv kev kho mob xws li Alzheimer's kab mob thiab gliomas. Receptor-kev kho mob transcytosis yog ib lub tswv yim zoo, thiab kev nce qib hauv cov thev naus laus zis tuaj yeem ua rau txoj hauv kev rau kev kho tshiab rau CNS cov teeb meem.
Prisys Biotech muaj kev tshaj lijNHP kab mob qauvthiab cov kev pabcuam dav dav hauv tsiaj tsiaj loj thiab kev tshawb fawb txog kev ua tau zoo los txhawb koj txoj kev tshawb fawb thiab kev tsim kho. Peb cov kev paub dhau los thiab cov qauv tshiab ua kom muaj txiaj ntsig zoo thiab kev twv ua ntej, pab txhawb kev txhais lus ntawm koj cov kev tshawb fawb biomedical. Yog xav paub ntxiv, thov mus saib peb lub vev xaib.
