Nhanganyaya kune mRNA mishonga
Messenger RNA (mRNA) inoteedzana nucleotides inoisa puroteni, uye mu cytoplasm inokwanisa kushandisa organelles kuratidza encoded protein. mRNA mishonga inogadziriswa nemakemikari zvichienderana nekusarudzwa kwezvinangwa kana maantigens uye kupinda mu cytoplasm kuburikidza nehurongwa hwekutakura (semuenzaniso, LNP), apo vanobudisa puroteni chaiyo (inoenderana nechinangwa chekugadzirwa kwemakemikari), uye mhedzisiro inoitika kana intracellularly kana mushure mekuvhara mukati me extracellular compartment (Fig. 1). Theoretically mRNA inogona kushandurirwa mune chero mapuroteni, uye chero mishonga inoshandisa mapuroteni sekurapa inogona kutsiviwa nemRNA marapiro.
Fig. 1. Mamiriro ezvinhu emishonga yemRNA uye nzira yavanoshandisa nayo kushanda kwayo.
Maitiro ezve pharmacokinetic zvidzidzo zvemRAN zvinodhaka
Nezve preclinical pharmacokinetic yekudzidza yemRNA mishonga, inogona kukamurwa kuita zvikamu zvitatu zvezvidzidzo zvakanangana nemRNA vaccines, mRNA therapeutics uye novel mishonga yemishonga. Zvinoenderana nejekiseni-inoenderana tekinoroji nhungamiro yakapihwa neFDA neNMPA, majekiseni kazhinji haadi zvechinyakare zvidzidzo zvepharmacokinetic, asi mamwe majekiseni akakosha anofanirwa kudzidzwa kuti biodistribution. Mishonga yemRNA ndeyemishonga yekudzivirira, inoda zvidzidzo zvebiodistribution. Uye iyo pharmacokinetic yekudzidza mRNA mishonga yekurapa inogona kubatsira kunzwisisa huwandu - hukama hwehukama hwemishonga. Kune mitsva yemishonga yemishonga, senge cationic lipids kana zvimwe zvinongedzo muLNP yekuunza masisitimu zvinhu zvitsva zvemishonga, in vitro, in vivo uye zvidzidzo zvekudyidzana kwezvinodhaka zvinodiwa zvinoenderana ne "Nhungamiro Yevasiri - Kuongororwa Kwekuchengetedza Kwekiriniki yeNew Pharmaceutical Excipients".Iyo in vitro yekudzidza ine metabolic kugadzikana uye metabolite kuzivikanwa kweakasiyana masisitimu, uye iyo in vivo kudzidza ine kunwisa, kugovera, metabolism uye zvidzidzo zvekubuda mumhuka kuona iyo in vivo ADME maitiro eanowana. Mushonga-kudyidzana kwezvinodhaka kwezvitsva zvinoongororwa kunoongororwa zvichienderana nehuwandu hwengozi.
IPHASE Inoenderana Zvigadzirwa
Messenger RNA (mRNA) inoteedzana nucleotides inoisa puroteni, uye mu cytoplasm inokwanisa kushandisa organelles kuratidza encoded protein. mRNA mishonga inogadziriswa nemakemikari zvichienderana nekusarudzwa kwezvinangwa kana maantigens uye kupinda mu cytoplasm kuburikidza nehurongwa hwekutakura (semuenzaniso, LNP), apo vanobudisa puroteni chaiyo (inoenderana nechinangwa chekugadzirwa kwemakemikari), uye mhedzisiro inoitika kana intracellularly kana mushure mekuvhara mukati me extracellular compartment (Fig. 1). Theoretically mRNA inogona kushandurirwa mune chero mapuroteni, uye chero mishonga inoshandisa mapuroteni sekurapa inogona kutsiviwa nemRNA marapiro.
Fig. 1. Mamiriro ezvinhu emishonga yemRNA uye nzira yavanoshandisa nayo kushanda kwayo.
Maitiro ezve pharmacokinetic zvidzidzo zvemRAN zvinodhaka
Nezve preclinical pharmacokinetic yekudzidza yemRNA mishonga, inogona kukamurwa kuita zvikamu zvitatu zvezvidzidzo zvakanangana nemRNA vaccines, mRNA therapeutics uye novel mishonga yemishonga. Zvinoenderana nejekiseni-inoenderana tekinoroji nhungamiro yakapihwa neFDA neNMPA, majekiseni kazhinji haadi zvechinyakare zvidzidzo zvepharmacokinetic, asi mamwe majekiseni akakosha anofanirwa kudzidzwa kuti biodistribution. Mishonga yemRNA ndeyemishonga yekudzivirira, inoda zvidzidzo zvebiodistribution. Uye iyo pharmacokinetic yekudzidza mRNA mishonga yekurapa inogona kubatsira kunzwisisa huwandu - hukama hwehukama hwemishonga. Kune mitsva yemishonga yemishonga, senge cationic lipids kana zvimwe zvinongedzo muLNP yekuunza masisitimu zvinhu zvitsva zvemishonga, in vitro, in vivo uye zvidzidzo zvekudyidzana kwezvinodhaka zvinodiwa zvinoenderana ne "Nhungamiro Yevasiri - Kuongororwa Kwekuchengetedza Kwekiriniki yeNew Pharmaceutical Excipients".Iyo in vitro yekudzidza ine metabolic kugadzikana uye metabolite kuzivikanwa kweakasiyana masisitimu, uye iyo in vivo kudzidza ine kunwisa, kugovera, metabolism uye zvidzidzo zvekubuda mumhuka kuona iyo in vivo ADME maitiro eanowana. Mushonga-kudyidzana kwezvinodhaka kwezvitsva zvinoongororwa kunoongororwa zvichienderana nehuwandu hwengozi.
IPHASE Inoenderana Zvigadzirwa
| Categories | Zvikamu |
| Subcellular fraction | chiropa lysosome |
| Acidified chiropa homogenate | |
| Chiropa/matumbu/itsvo/mapapu S9 | |
| Chiropa/mudumbu/itsvo/mapapu microsomes | |
| Chiropa/mudumbu/renal/mapapu cytoplasmic fluid | |
| Primary Hepatocytes | Kumiswa kweHepatocytes |
| Platable Hepatocytes | |
| Exclusive plasma | Plasma kugadzikana |
| Plasma protein inosunga | |
| Ropa rose | Munhu/Tsoko/Canine/Gonzo/Mbeva/Tsuro/Nguruve Ropa Rakazara |
Nguva yekutumira: 2024-08-25 19:54:01