Ingabe i-Gene Therapy iyindlela eya empilweni ye-HIV?

I-HIV eyenziwa ngabantu abayizikhukhula ze-HIV Ukuhlasela Amaphuzu Okudumayo

Abacwaningi abavela eHarvard Medical School naseScripps Research Institute eFlorida bamemezele ukuthi i-gene therapy ye-gene, ehlinzekwe nge-intramuscularly, ivimbele ngokuphumelelayo ukudluliselwa kwe- HIV-1 ne-HIV-2 eqenjini lezinkabi ze-macaque ezivezwe kaningi kwigciwane. Ukutholakala kubonakala njengesinyathelo sokuqala ekuthuthukiseni ukhetho lokugoma oluzokwazi ukunikeza ukuvikela okufanayo kubantu.

Abacwaningi baseHarvard ne-Scripps bakwazi ukuthuthukisa i-molecule eyakhiwe nge-lab ebizwa ngokuthi i- eCD4-Ig , efanisa izinhlobo ezimbili zamaprotheni amatholampilo atholakalayo ebusweni bamangqamuzana egazi omhlophe ukuthi i- HIV ihambisana nokutheleleka ngesikhathi sokutheleleka. Ngokwenza kanjalo, i-HIV "ikhohlisiwe" ekuziqhenyeleni ekwakheni izakhi zofuzo, ngaleyo ndlela iwuqede.

Yeka kanjani i-eCD4-Ig Works

I-eCD4-Ig yenziwe i- CD4 kanye nengxenye yeCCR5 -iyo yesikhombimsebenzisi esithatha isenzo sokungena "ukukhiya" esitokisini-okuhlangene ndawonye ku-piece of antibody . Ukwakhiwa kwezakhi zofuzo bese kufakwa ku-adenovirus (uhlobo lwegciwane elingenalo isifo), elinikezwa ngqo emathisini omzimba. Lapho lapho, igciwane elingenakulimala ngokushesha lihlasela amangqamuzana, kufaka i-DNA yalo kwinucleus, futhi iguqula ibe amaprotheni amakhomikhali-ahlaziye kakhulu la ma antibodies alungisiwe.

Imizamo yangaphambilini yokuqasha "i-CD4-Ig" engaxhunywanga (okungukuthi, ngaphandle kwesiqeshana se-CCR5) iphumelele kancane kancane.

Kwamanye amacala, uma izingxube ze-antibodies eziguquliwe zazingaphansi kakhulu, umsebenzi we-HIV wawuzokhuliswa kuphela. Lokhu kungenxa yokuthi i-HIV yakwazi ukuphunyuka kwe-neutralization ngokwanele ukuze iguqule futhi ibophe kuma-receptors.

Ngenkathi i-HIV isakwazi ukuphunyuka futhi iguqule phambi kwe-ECD4-Ig, i-bivalent (okungukuthi, ehlanganisa ukusethwa kwama-chromosomes amabili) kubonakala sengathi kubeka izindleko ezinkulu kwigciwane eliguquguqukayo, ukunciphisa kakhulu ikhono layo lokuphindaphinda.

Ezifundweni zabo ezilawulwa yizilwane, abacwaningi babike ukuthi izimbongolo ezifakelwe i-adenovirus ezakhiwe ngokofuzo zikwazi ukuvimbela yonke imithi ye-HIV-1, i-HIV-2 ne-SIV (uhlobo olufanayo lwe-HIV), ngisho nangemva kokujova ngokuphindaphindiwe ngamanani aphezulu igciwane lamaviki angu-40. Ayikho enye yezinkawu ezingenayo i-HIV, futhi akekho owenza umphumela omubi ku-eCD4-Ig (mhlawumbe ngoba imizimba yabo yaqaphela ukuthi amaprotheni ayilona eyabo).

Izinkabi azizange zinikezwe i-eCD4-Ig inoculate bonke ababenesifo.

Kusho Ukuthini Konke Lokhu?

Ngesikhathi kusesekuseni kakhulu ukukhombisa ukuthi ukuhlolwa kubantu kuzokwenza imiphumela efanayo, indlela iveza isu elingase liguqule umdlalo ekuthuthukiseni umuthi wokugoma we-HIV .

Abanye sebevele baqala ukucabanga ukuthi ukuthuthukiswa komgomo ophumelelayo we-ECD4-Ig, osebenza ngokuphumelelayo esikhathini eside, kungase kusebenze ekunciphiseni umsebenzi wegciwane lesandulela ngculaza, kungaba yedwa noma namanye ama-agent. Uma lokhu, eqinisweni, kufinyeleleka, ngakho-ke ngisho neziguli ezinokumelana nokujulile kwezidakamizwa ezijulile zingase zizuze.

Noma kunjalo, konke lokhu kuhlala kucabangela kakhulu. Ucwaningo olwengeziwe luzohlinzeka ngokuqonda okukhulu ezinyangeni ezizayo, okukhomba indlela eya kuhlolwa kwesilingo esisekuseni.

Olunye uhlobo lweNvelidi Yokufinyelela ku-Gene Therapy

Ngaphandle kokucwaninga kweHarvard / Scripps, omunye usosayensi ubheke ezinye izindlela zokuhlela izakhi ukuze alwe noma avimbele ukutheleleka nge-HIV.

Enye imodeli enjalo evela ososayensi eThekwini University ithola ama-T-cells aphethwe yi-T-cells egazini likagulane futhi isebenzisa i-enzyme ebizwa ngokuthi i- Cas9 ukuze "idonsa" izinto ezivela ku-DNA yesitokisi. Ngokwenza kanjalo, amangqamuzana akakwazi ukutheleleka nge-HIV.

Kuthiwa ukuthi ngokujova lawa maseli emzimbeni wesiguli, ikhono le-HIV lokutheleleka lizokwehliswa kakhulu, linciphise ukuqhuma kwesifo ngenkathi ivumela amangqamuzana avuselelwe ukuba abe yingxenye yomzimba womuntu (i-genetic makeup).

Ngokufanayo, ososayensi e-UCLA bahlola ukusetshenziswa kwe-molecule enjini okuthiwa i- CAR (chimeric antigen receptor), ekwazi ukuguqula noma iyiphi i-cell cell kwisilonda segazi elimhlophe. Ngokufaka i-CAR zibe amangqamuzana e-blood stem, aba ososayensi bakwazi ukuguqula amangqamuzana abe yizinhlobo ezithile zokubulala ezidingekayo ukuze kulungiswe i-HIV-free-circulating.

Ngenkathi kokubili izifundo zikhona esikhungweni se-tube test, lokho okutholwa kubhekwa njengento ebalulekile ekuthuthukiseni ukhetho lokugomela igciwane lesandulela ngculazi.

Imithombo:

Gardner, M .; Kattenhorn, L .; I-Kondur, H .; et al. "I-AAV-Express CD4-Ig inikeza ukuvikelwa okuqinile kwezinselele eziningi ze-SHIV." Imvelo. Ngo-February 18, 2015; i-doi: 10.1038 / imvelo14264.

I-Kaminski, R; I-Chen, i-Y .; Tedaldi, E .; et al. "Ukuqedwa kwama-genomes we-HIV-1 kusuka kumangqamuzana angama-T-lymphoid yi-CRISPR / Cas9 ye-gene editing." Imvelo . Mashi 4, 2016; eshicilelwe ku-DOI: 10.1038 / srep22555.

I-Zhen, A .; Kamata, M .; URezek, V. et al. "Ukungenwa Kakhulu Kwegciwane lesandulela-ngculazi Kwenziwe Ngama-Stem Amaseli E-Symeric Receptor-engineered." Ukwelashwa Kwama-molecular. Agasti 2015; 23 (80): 1358-1367.