Okwu mmalite nke ọgwụ mRNA
Messenger RNA (mRNA) bụ usoro nucleotides nke na-etinye protein, na cytoplasm na-enwe ike iji organelles gosipụta protein ahụ etinyere. A na-emezi ọgwụ mRNA nke kemịkalụ dabere na nhọrọ nke ebumnuche ma ọ bụ antigens wee banye na cytoplasm site na usoro nnyefe a kapịrị ọnụ (dịka ọmụmaatụ, LNP), ebe ha na-emepụta protein dị iche iche (nke kwekọrọ na ebumnuche nke nhazi mgbanwe kemịkalụ), mmetụta ahụ na-eme ma ọ bụ intracellular ma ọ bụ mgbe nzuzo zoro n'ime oghere extracellular (Fig 1). Enwere ike ịtụgharị mRNA ka ọ bụrụ protein ọ bụla, ma ọgwụ ọ bụla na-eji protein dị ka ọgwụgwọ nwere ike iji usoro ọgwụgwọ mRNA dochie ya.
Fig. 1. Atụmatụ nhazi nke ọgwụ mRNA na usoro ha si arụ ọrụ ha.
Atụmatụ maka ọmụmụ ọgwụ pharmacokinetic nke ọgwụ mRAN
Banyere ọmụmụ ọgwụ ọgwụ preclinical nke ọgwụ mRNA, enwere ike kewaa ya n'akụkụ atọ nke ọmụmụ na-eche ọgwụ mgbochi mRNA, ọgwụgwọ mRNA na ihe mgbakwunye ọgwụ ọhụrụ. Dika ogwu ogwu - ntuziaka oru ngo emetụtara nke FDA na NMPA nyere, ogwu ogwu adighi acho ihe omumu ogwu ogwu oge nile, mana ekwesiri imuta ufodu ogwu ogwu puru iche maka ikesa biodistribution. Ọgwụ mgbochi mRNA bụ nke ọgwụ mgbochi pụrụ iche, nke chọrọ ọmụmụ nkesa biodistribution. Na ọmụmụ pharmacokinetic nke ọgwụ ọgwụgwọ mRNA nwere ike inye aka ịghọta oke-mmekọrịta ọgwụ. Maka ihe mgbakwunye ọgwụ ọhụrụ, dị ka cationic lipids ma ọ bụ ihe ndị ọzọ dị na sistemụ nnyefe LNP bụ ihe ọhụrụ ọgwụ ọhụrụ, in vitro, in vivo na ọmụmụ mmekọrịta ọgwụ dị ka "Ntuziaka maka Ntụle Nchekwa Ahụike nke Ndị Ọhụrụ Pharmaceutical Excipients".Ọmụmụ ihe in vitro nwere nkwụsi ike nke metabolic na njirimara metabolite nke sistem dị iche iche, na ọmụmụ ihe in vivo nwere absorption, nkesa, metabolism na excretion ọmụmụ n'ime ụmụ anụmanụ iji chọpụta usoro in vivo ADME nke onye na-eme ihe. A na-enyocha mmekọrịta ọgwụ na ọgwụ ọhụrụ nke ndị ọhụrụ na-adabere n'ogo nke ihe ize ndụ.
Ngwaahịa metụtara IPHASE
Messenger RNA (mRNA) bụ usoro nucleotides nke na-etinye protein, na cytoplasm na-enwe ike iji organelles gosipụta protein ahụ etinyere. A na-emezi ọgwụ mRNA nke kemịkalụ dabere na nhọrọ nke ebumnuche ma ọ bụ antigens wee banye na cytoplasm site na usoro nnyefe a kapịrị ọnụ (dịka ọmụmaatụ, LNP), ebe ha na-emepụta protein dị iche iche (nke kwekọrọ na ebumnuche nke nhazi mgbanwe kemịkalụ), mmetụta ahụ na-eme ma ọ bụ intracellular ma ọ bụ mgbe nzuzo zoro n'ime oghere extracellular (Fig 1). Enwere ike ịtụgharị mRNA ka ọ bụrụ protein ọ bụla, ma ọgwụ ọ bụla na-eji protein dị ka ọgwụgwọ nwere ike iji usoro ọgwụgwọ mRNA dochie ya.
Fig. 1. Atụmatụ nhazi nke ọgwụ mRNA na usoro ha si arụ ọrụ ha.
Atụmatụ maka ọmụmụ ọgwụ pharmacokinetic nke ọgwụ mRAN
Banyere ọmụmụ ọgwụ ọgwụ preclinical nke ọgwụ mRNA, enwere ike kewaa ya n'akụkụ atọ nke ọmụmụ na-eche ọgwụ mgbochi mRNA, ọgwụgwọ mRNA na ihe mgbakwunye ọgwụ ọhụrụ. Dika ogwu ogwu - ntuziaka oru ngo emetụtara nke FDA na NMPA nyere, ogwu ogwu adighi acho ihe omumu ogwu ogwu oge nile, mana ekwesiri imuta ufodu ogwu ogwu puru iche maka ikesa biodistribution. Ọgwụ mgbochi mRNA bụ nke ọgwụ mgbochi pụrụ iche, nke chọrọ ọmụmụ nkesa biodistribution. Na ọmụmụ pharmacokinetic nke ọgwụ ọgwụgwọ mRNA nwere ike inye aka ịghọta oke-mmekọrịta ọgwụ. Maka ihe mgbakwunye ọgwụ ọhụrụ, dị ka cationic lipids ma ọ bụ ihe ndị ọzọ dị na sistemụ nnyefe LNP bụ ihe ọhụrụ ọgwụ ọhụrụ, in vitro, in vivo na ọmụmụ mmekọrịta ọgwụ dị ka "Ntuziaka maka Ntụle Nchekwa Ahụike nke Ndị Ọhụrụ Pharmaceutical Excipients".Ọmụmụ ihe in vitro nwere nkwụsi ike nke metabolic na njirimara metabolite nke sistem dị iche iche, na ọmụmụ ihe in vivo nwere absorption, nkesa, metabolism na excretion ọmụmụ n'ime ụmụ anụmanụ iji chọpụta usoro in vivo ADME nke onye na-eme ihe. A na-enyocha mmekọrịta ọgwụ na ọgwụ ọhụrụ nke ndị ọhụrụ na-adabere n'ogo nke ihe ize ndụ.
Ngwaahịa metụtara IPHASE
| Otu | Nhazi |
| Iberibe subcellular | imeju lysosome |
| Acidified imeju homogenate | |
| Imeju/eriri afọ/akụrụ/akpa ume S9 | |
| Umeji / eriri afọ / akụrụ / akpa ume microsomes | |
| Mmiri cytoplasm nke imeju / eriri afọ / gbasara akụrụ | |
| Hepatocytes nke mbụ | Hepatocytes nkwusioru |
| Hepatocytes nke nwere ike ime | |
| Plasma pụrụ iche | Nkwụsi ike Plasma |
| Plasma njikọ protein | |
| Ọbara dum | Mmadu/enwe/Mkpụrụkpụ/oke/oke/oke oke oyibo/ezi oghere zuru oke |
Oge nzipu: 2024-08-25 19:54:01