Taw qhia rau cov tshuaj mRNA
Neeg xa xov liaison RNA (mRNA) yog ib theem ntawm nucleotides uas encodes ib tug protein, thiab nyob rau hauv lub cytoplasm muaj peev xwm siv organelles qhia cov encoded protein. mRNA tshuaj raug hloov kho raws li kev xaiv ntawm lub hom phiaj lossis antigens thiab nkag mus rau cytoplasm los ntawm kev xa khoom tshwj xeeb (piv txwv li, LNP), qhov chaw uas lawv tsim cov protein tshwj xeeb (raws li lub hom phiaj ntawm kev hloov kho tshuaj), thiab cov nyhuv tshwm sim los ntawm intracellularly lossis tom qab tso rau hauv lub cell sab nraud (Daim duab 1). Raws li txoj cai, mRNA tuaj yeem muab txhais ua ib qho protein, thiab txhua yam tshuaj uas siv cov proteins raws li kev kho mob tuaj yeem hloov tau los ntawm kev kho mRNA.
Fig. 1. Cov yam ntxwv ntawm mRNA cov tshuaj thiab cov txheej txheem uas lawv siv lawv cov kev ua tau zoo
Cov tswv yim rau kev tshawb fawb pharmacokinetic ntawm mRAN tshuaj
Hais txog kev tshawb fawb pharmacokinetic preclinical ntawm mRNA tshuaj, nws tuaj yeem muab faib ua peb feem ntawm kev tshawb fawb tsom rau cov tshuaj tiv thaiv mRNA, mRNA kho thiab cov tshuaj tshiab tshiab. Raws li cov tshuaj tiv thaiv - ntsig txog cov txheej txheem qhia tawm los ntawm FDA thiab NMPA, cov tshuaj tiv thaiv feem ntau tsis tas yuav muaj kev tshawb fawb pharmacokinetic niaj hnub, tab sis qee cov tshuaj tiv thaiv tshwj xeeb yuav tsum tau kawm rau biodistribution. Cov tshuaj tiv thaiv mRNA yog cov tshuaj tiv thaiv tshwj xeeb, uas yuav tsum muaj kev tshawb fawb txog biodistribution. Thiab kev tshawb fawb pharmacokinetic ntawm mRNA cov tshuaj kho mob tuaj yeem pab kom nkag siab txog qhov muaj nuj nqis - cuam tshuam kev sib raug zoo ntawm cov tshuaj. Rau cov khoom siv tshuaj tshiab, xws li cationic lipids lossis lwm cov khoom xyaw hauv LNP cov tshuab xa khoom yog cov tshuaj tshiab, hauv vitro, hauv vivo thiab cov kev tshawb fawb tshuaj sib cuam tshuam yuav tsum tau ua raws li "Cov Lus Qhia rau Kev Ntsuam Xyuas Kev Nyab Xeeb Kev Nyab Xeeb ntawm Cov Tshuaj Tshiab Tshiab".Txoj kev tshawb fawb hauv vitro muaj cov metabolism hauv kev ruaj ntseg thiab kev txheeb xyuas cov metabolite ntawm ntau lub tshuab, thiab hauv vivo txoj kev tshawb fawb muaj kev nqus, kev faib tawm, kev tshawb fawb metabolism thiab kev tso tawm hauv cov tsiaj los txiav txim siab hauv vivo ADME txheej txheem ntawm excipient. Tshuaj - tshuaj sib cuam tshuam ntawm cov khoom ntxiv tshiab raug tshuaj xyuas nyob ntawm qib ntawm kev pheej hmoo.
IPHASE cov khoom lag luam
Neeg xa xov liaison RNA (mRNA) yog ib theem ntawm nucleotides uas encodes ib tug protein, thiab nyob rau hauv lub cytoplasm muaj peev xwm siv organelles qhia cov encoded protein. mRNA tshuaj raug hloov kho raws li kev xaiv ntawm lub hom phiaj lossis antigens thiab nkag mus rau cytoplasm los ntawm kev xa khoom tshwj xeeb (piv txwv li, LNP), qhov chaw uas lawv tsim cov protein tshwj xeeb (raws li lub hom phiaj ntawm kev hloov kho tshuaj), thiab cov nyhuv tshwm sim los ntawm intracellularly lossis tom qab tso rau hauv lub cell sab nraud (Daim duab 1). Raws li txoj cai, mRNA tuaj yeem muab txhais ua ib qho protein, thiab txhua yam tshuaj uas siv cov proteins raws li kev kho mob tuaj yeem hloov tau los ntawm kev kho mRNA.
Fig. 1. Cov yam ntxwv ntawm mRNA cov tshuaj thiab cov txheej txheem uas lawv siv lawv cov kev ua tau zoo
Cov tswv yim rau kev tshawb fawb pharmacokinetic ntawm mRAN tshuaj
Hais txog kev tshawb fawb pharmacokinetic preclinical ntawm mRNA tshuaj, nws tuaj yeem muab faib ua peb feem ntawm kev tshawb fawb tsom rau cov tshuaj tiv thaiv mRNA, mRNA kho thiab cov tshuaj tshiab tshiab. Raws li cov tshuaj tiv thaiv - ntsig txog cov txheej txheem qhia tawm los ntawm FDA thiab NMPA, cov tshuaj tiv thaiv feem ntau tsis tas yuav muaj kev tshawb fawb pharmacokinetic niaj hnub, tab sis qee cov tshuaj tiv thaiv tshwj xeeb yuav tsum tau kawm rau biodistribution. Cov tshuaj tiv thaiv mRNA yog cov tshuaj tiv thaiv tshwj xeeb, uas yuav tsum muaj kev tshawb fawb txog biodistribution. Thiab kev tshawb fawb pharmacokinetic ntawm mRNA cov tshuaj kho mob tuaj yeem pab kom nkag siab txog qhov muaj nuj nqis - cuam tshuam kev sib raug zoo ntawm cov tshuaj. Rau cov khoom siv tshuaj tshiab, xws li cationic lipids lossis lwm cov khoom xyaw hauv LNP cov tshuab xa khoom yog cov tshuaj tshiab, hauv vitro, hauv vivo thiab cov kev tshawb fawb tshuaj sib cuam tshuam yuav tsum tau ua raws li "Cov Lus Qhia rau Kev Ntsuam Xyuas Kev Nyab Xeeb Kev Nyab Xeeb ntawm Cov Tshuaj Tshiab Tshiab".Txoj kev tshawb fawb hauv vitro muaj cov metabolism hauv kev ruaj ntseg thiab kev txheeb xyuas cov metabolite ntawm ntau lub tshuab, thiab hauv vivo txoj kev tshawb fawb muaj kev nqus, kev faib tawm, kev tshawb fawb metabolism thiab kev tso tawm hauv cov tsiaj los txiav txim siab hauv vivo ADME txheej txheem ntawm excipient. Tshuaj - tshuaj sib cuam tshuam ntawm cov khoom ntxiv tshiab raug tshuaj xyuas nyob ntawm qib ntawm kev pheej hmoo.
IPHASE cov khoom lag luam
| Pawg | Kev faib tawm |
| Subcellular feem | lub siab lysosome |
| Acidified daim siab homogenate | |
| Lub siab / plab hnyuv / raum / ntsws S9 | |
| Lub siab / plab hnyuv / raum / ntsws microsomes | |
| Lub siab / plab hnyuv / raum / ntsws cytoplasmic kua | |
| Primary Hepatocytes | Ncua Hepatocytes |
| Platable Hepatocytes | |
| Tshwj xeeb plasma | Plasma stability |
| Plasma protein khi | |
| Cov ntshav tag nrho | Tib neeg / Liab / Canine / Nas / Nas / Luav / Pig Blank Whole Blood |
Hnub tim: 2024-08-25 19:54:01