Lysosomes (Tritosomes): He ʻōnaehana hoʻāʻo i loko o ka vitro no ka catabolism a i ʻole nā haʻawina paʻa lysosomal.

Nā huahana IPHASE

Hoʻolauna iLysosomes
Ua ʻike ʻia ka lysosome e Christian deDuve i ka makahiki 1950 a ua hoʻokumu ʻia ma ke ʻano he kikowaena o ka degradation a me ka metabolism i loko o ke kelepona. ʻO nā Lysosomes hoʻokahi-membrane, dynamic, heterogeneous organelles i ʻokoʻa i ka wahi, morphology, nui, ʻike enzyme, a me nā substrates. Aia i loko o ka membrane lysosomal he mau haneli o nā protein membrane peripheral, me nā ʻano like ʻolenā mea halihalia me nā awāwa ion. Mālama ka lysosomal multi-subunit V-ATPase i ka lumen lysosomal acidic. ʻO kēia pH haʻahaʻa (4.5 - 5.5) e hoʻāla i ka> 50 lysosomal hydrolases e ʻeli i nā macromolecules me nā protein, nucleic acids, lipids, a me nā kalapona. Loaʻa a ʻeli ʻo Lysosomes i nā molekole liʻiliʻi a me nā mea endocytosed, e hoʻopau i nā mea nui e like me nā apoptotic cell corpses a me pathogenic bacteria, a i ʻole autophagocytose cytoplasmic contents, me ka mitochondria poino, endoplasmic reticulum, a me nā lysosomes. No laila, ua manaʻo ʻia nā lysosomes i ka "recycling bin" o ke kelepona.

Tritosome

ʻO Tritosomes nā hale subcellular kūikawā e pili ana i nā kaʻina cellular like ʻole, ʻoi loa i ka hoʻoponopono ʻana i nā ala metabolic a me ka mālama ʻana i ka homeostasis cellular. Hoʻomaʻamaʻa pinepine ʻia nā tritosomes i ka pōʻaiapili o kā lākou kuleana i loko o nā kumu hoʻohālike kino. ʻO ka hiʻohiʻona wehewehe o kēia mau hale ʻo kā lākou haku mele ʻana, e hiki ai iā lākou ke hana i nā hana koʻikoʻi e koʻikoʻi no ke ola ʻana a me ka hana pono o nā cell. ʻO nā tritosomes ate ʻiole nā lysosomes hepatic i hoʻouka ʻia me Tyloxapol (Triton WR 1339), kahi mea hoʻoheheʻe non-ionic. ʻO nā lysosomes i loaʻa ka tylosapol e hōʻike ana i ka liʻiliʻi liʻiliʻi, hiki ke hoʻokaʻawale maikaʻi ʻia mai ka mitochondria, a hoʻohaumia i nā organelles i uhi ʻia me nā lysosomal densities maoli.

Hoʻohana i nā lysosomes
· Nā lāʻau liʻiliʻi nucleic acid a me nā lysosomes
ʻO nā lāʻau lapaʻau liʻiliʻi nucleic acid e pili ana i nā ʻāpana liʻiliʻi o nā nucleotides me nā kaʻina kikoʻī e hiki ke hoʻopaʻa i nā mRNA kikoʻī a keʻakeʻa i ka pono unuhi o nā mRNA e hoʻokō i nā hopena therapeutic. ʻO nā lāʻau liʻiliʻi nucleic acid he antisense oligonucleotides (ASOs), RNA interfering liʻiliʻi (siRNA), microRNA (miRNA), RNA aptamers, a me nā mea ʻē aʻe.

Ma hope o ka lawelawe ʻana, pono mua nā lāʻau nucleic acid e pale i ka degradation e nā nucleases i loko o ka plasma a me nā ʻiʻo, hopu ʻia e ka ʻōnaehana pale, hiki i ka ʻiʻo i hoʻopaʻa ʻia, komo i ka cell ma o endocytosis, a pakele ma mua o ka hui ʻana o ka endosome me ka lysosome, e komo i ka cytoplasm, a hui pū me ka mRNA i hoʻopaʻa ʻia e hoʻokō i ka gene silencing, a laila e hoʻokō ai i ka lāʻau efficacy. Hiki ke hoʻohana ʻia nā Lysosomes ma ke ʻano he ʻōnaehana hoʻāʻo maikaʻi e loiloi i nā loli i ka paʻa o nā lāʻau nucleic acid liʻiliʻi i hoʻololi ʻia ma hope o ka hana ʻana o nā lysosomes in vitro, e hāʻawi ana i ke kākoʻo ʻikepili no ka noiʻi ʻana i nā waikawa nucleic liʻiliʻi.

· Antibody-drug conjugate (ADC) a me nā lysosomes
ʻO Antibody-drug conjugate (ADC) kahi ʻano hou o ka lāʻau biotechnology e hoʻohui i nā pūhui mole liʻiliʻi i nā antibodies i kuhikuhi ʻia a i ʻole nā ʻāpana antibody ma o nā loulou. Hiki iā ia ke hoʻonui i ka huli ʻana i ka lāʻau lapaʻau a me ke kūpaʻa, e hōʻemi i ka lāʻau lapaʻau a me nā hopena ʻaoʻao, a hoʻomaikaʻi i ka therapeutic index. Loaʻa iā ia ka hopena pepehi o nā lāʻau mole liʻiliʻi liʻiliʻi a me ka huli ʻana i nā lāʻau antibody. Hoʻohana nui ʻia i ka mālama ʻana i ka anti-tumor a i ʻole nā ​​​​maʻi ʻē aʻe.

Ma hope o ke komo ʻana i ke kino, hiki i nā molekala ADC ke hoʻopaʻa i nā antigens ma ka ʻili o nā cell target ma o ke alakaʻi ʻana o nā antibodies monoclonal, a hoʻololi hou i loko o nā cell target. Hiki i nā moleke ADC ke komo i loko o nā pūnaewele (ma ka nui o nā lysosomes) hiki ke hoʻokuʻu i nā moleke liʻiliʻi liʻiliʻi a me / a i ʻole nā ​​mea hoʻohālikelike toxin (ʻo ia hoʻi, nā moleke effector) ma o ka hana kemika a/a i ʻole enzymatic e "pepehi" i nā pūnaewele. Pono ʻo ADC i nā lysosomes hana e hoʻoheheʻe a hoʻokuʻu i nā lāʻau mole liʻiliʻi e hoʻohana i ko lākou pono, e komo i loko o ka membrane lysosomal a i ʻole ka lawe ʻana i waho o nā lysosomes, a e launa pū me nā pahu molekala i loko o ka cytoplasm a i ʻole nucleus. Hiki i nā hoʻokolohua in vitro o ADC a me nā lysosomes ke loiloi inā hiki ke ʻoki maikaʻi ʻia ka loulou e nā lysosomes e hoʻokuʻu i nā lāʻau mole liʻiliʻi e lawe ai, e hāʻawi ana i kahi mea loiloi in vitro no ka hoʻolālā ʻana i nā loulou ADC.

No IPHASE
Ma ke ʻano he alakaʻi alakaʻi o ka in vitro biological reagents no ka hoʻomohala ʻana i ka lāʻau lapaʻau, ua hoʻokumu ʻo IPHASE i nā huahana lysosome ate o nā ʻano ʻelima, e like me ke kanaka, ka monkey, ka ʻīlio, ka ʻiole a me ka ʻiole, ma o ka hoʻomau ʻana a me ka hoʻāʻo ʻana, e hilinaʻi ana i kāna ʻoihana R&D a me ka hui hana e kōkua i ka hoʻomohala lāʻau.
· Ka hana enzyme kiʻekiʻe: Ua hoʻāʻo ʻia nā lysosomes ate IPHASE no ka cathepsin B a me ka hana acid phosphatase, a ua hoʻohālikelike ʻia ka hana enzyme a ʻoi aku paha ma mua o nā huahana like i lawe ʻia mai.
· Hoʻokumu pūʻulu: Hoʻohana ʻia ka hana ʻana o ka hui, a lawa ka waihona e hōʻoia i ka hoʻolako ʻana i ka pūʻulu like o nā huahana.
· Ka manawa hāʻawi pōkole: Ka noiʻi kūʻokoʻa a me ka hoʻomohala ʻana, nā hale kūʻai he nui i ka waihona, e hōʻoia i ka pono o ka mea kūʻai aku.