Tekinoroji dzeBiomedical muKutsvagurudza HIV
Kutsvagurudza nezveHIV kwafambira mberi zvikuru kubvira pakatanga kuonekwa hutachiona uhwu pakutanga kwema1980. Tekinoroji yezvekurapa yave iri simba guru rekuenderera mberi uku—kubva pakuongorora nekukurumidza uye kwakarurama uye kugadzira marongerwo ehutachiona kusvika pakugadzirwa kwemishonga yekurwisa HIV (ARV) inoshanda zviri nani. Nhasi, tekinoroji yezvekurapa haingobatsiri masayendisiti kunzwisisa kuti HIV inotapukira sei mumuviri asiwo inovhura mukana wekudzivirira kwakasimba uye, kwenguva refu, nzira dzekurapa kunoshanda. Chinyorwa chino chinoongorora matekinoroji ezvekurapa akakosha pakutsvagurudza nezveHIV.
1. Kuongorora kwemazuva ano: kubva pakuonekwa kwemasoja ekudzivirira chirwere kusvika pakuongororwa kwemamorekuru
Chimwe chezvinhu zvakakosha mumhinduro yeHIV kwave kuri kuvandudzwa kwekugona kuona HIV nekukurumidza. Pakutanga kwedenda, kuongororwa kwacho kwainyanya kuenderana nekuona ma antibodies, izvo zvinotora nguva nekuti muviri unoda nguva yakati kuti uve nemhinduro yekudzivirira chirwere. Iye zvino, matekinoroji akasiyana-siyana ekurapa anobvumira kuonekwa nekukurumidza nekunzwisisa kwakanyanya.
Semuenzaniso, bvunzo dzechizvarwa chechina dzinogona kuona ma antibodies pamwe ne p24 antigen, puroteni yeHIV inoonekwa nguva pfupi yadarika mushure mekutapukirwa. Uyezve, matekinoroji ekuongorora mamorekuru akadai se PCR (polymerase chain reaction) anobvumira kuona zvakananga majini ehutachiona. PCR inobatsira zvikuru pakuona hutachiona pakutanga, kutarisa huwandu hwehutachiona muropa, uye kuongorora kushanda kwemishonga yeARV.
Kufambira mberi pakuongorora chirwere kunoonekwawo mukugadzirwa kwemiedzo inokurumidza inogona kushandiswa munzvimbo dzehutano dzisina zviwanikwa zvakawanda. Nekushandisa nzira yekutarisira varwere, vanhu vanogona kuwana mhedzisiro nekukurumidza, vachikurumidzisa mazano, kutumirwa kune vamwe varwere, uye kurapwa.
2. Kutevedzana kwezviitiko uye bioinformatics: kunzwisisa kushanduka kweHIV nekusiyana-siyana
HIV inozivikanwa nekuva nehuwandu hwakawanda hwekuchinja kwemasero. Hunhu uhwu hunoita kuti hutachiona hukwanise kuchinja nekukurumidza, kusanganisira kubuda kwekusakwanisa kushandisa mishonga. Tekinoroji dzekuongorora masero - Sanger sequencing uye next-generation sequencing (NGS) - dzinobvumira vaongorori kuverenga genetic sequence yeHIV, kuongorora kushanduka kwemasero, uye kuronga hukama huripo pakati pemarudzi akasiyana.
Nekushandisa NGS, vaongorori vanogona kuona huwandu hudiki hwemavhairasi hungave husingaonekwe nenzira dziri nyore asi hune mukana wekushanduka hukava mhando huru sezvo kumanikidzwa kwemishonga kuchiwedzera. Kutevedzana kwedata kunobatsirawo pakuongorora epidemiological: kutevera maitiro ekupararira kwechirwere, kuona mapoka, uye kunzwisisa mafambiro echirwere munzvimbo.
Bioinformatics ine basa guru mukugadzirisa data iri rakakura. Maitiro ekushandisa anoshandiswa kufanotaura kukanganisa kwekuchinja kwemapuroteni ehutachiona, kuona mishonga mitsva, uye kuratidza kuti hutachiona hunoshanduka sei muvarwere. Kusanganiswa kweNGS ne bioinformatics ikozvino kwave chinhu chakakosha mukutsvagisa kweHIV kwemazuva ano.
3. Kukura kwemasero uye mamodheru emu vitro: kuyedza nzira dzehutachiona uye nzira dzekurapa dzinodiwa
Tekinoroji yekukura kwemasero inoita kuti pave nezvidzidzo zvakadzama zvehupenyu hweHIV. Vaongorori vanoshandisa masero avanoda kuita akadai seCD4+ T lymphocytes kana macrophages kuti vadzidze kuti hutachiona hunobatana sei, hunopinda sei, hunoberekana sei, uye hunodzivisa sei immune system. Nekushandisa ma in vitro systems, mishonga yakasiyana-siyana inogona kuongororwa pasi pemamiriro ezvinhu akarongwa vasati vapinda mumiedzo yemhuka kana yekiriniki.
Kuwedzera patsika dzemazuva ano dzemasero, tekinoroji ye organoid uye masisitimu e microfluidic (dzimwe nguva anonzi organs-on-a-chip) ari kutanga kushandiswa kutevedzera zviri kuitika munzvimbo yenyama yemunhu. Izvi zvakakosha nekuti HIV inogona kuramba iripo munzvimbo dzakachengetwa, kusanganisira lymphoid tissue. Mamodheru anotevedzera zvakanyanya biology yemunhu anobatsira vaongorori kuongorora kupinda kwemishonga, mhinduro dzemuviri dzemuno, uye zvinhu zvinopesvedzera kuramba kuripo kwehutachiona.
4. Matekinoroji ekugadzira mishonga: kubva pakuongorora zvinhu zvakawanda kusvika pakugadzira zvinhu zvinoenderana nechimiro
Kugadzirwa kwemishonga yeARV ndeimwe yekubudirira kukuru kwehunyanzvi hwekurapa. Nhasi uno, mishonga yekubatanidza inogona kuderedza huwandu hwehutachiona kusvika padanho risingaonekwe, kuwedzera hupenyu hwemunhu, uye kuderedza njodzi yekutapurirana. Mukutsvaga mishonga yeHIV, kuongorora kwakanyanya (HTS) kunoshandiswa kuyedza nekukurumidza zviuru kusvika kumamiriyoni emishonga kuti vawane mishonga inodzivisa ma enzymes kana maitiro ehutachiona.
Pamusoro peHTS, dhizaini yemushonga yakavakirwa pachimiro inoshandisa nzira dzakadai seX-ray crystallography, NMR, uye cryo-electron microscopy kuti iwane mifananidzo yakadzama yemaumbirwo emapuroteni eHIV. Neruzivo urwu, masayendisiti anogona kugadzira mamorekuru "anokodzera" uye anodzivisa kushanda kwemapuroteni akakosha, akadai sereverse transcriptase, protease, integrase, kana mapuroteni ane chekuita nekupinda kwehutachiona mumasero.
Imwe nzira inokosha iripo ndeyekugadzirwa kwemishonga inoshanda kwenguva refu—mishonga inobayiwa jekiseni kana inoiswa mumuviri inoshanda kwemavhiki kusvika kumwedzi. Tekinoroji yekugadzira mishonga uye masisitimu ekupa mishonga zvakakosha pakuona kuti huwandu hwemishonga mumuviri hwakagadzikana.
5. Tekinoroji yekudzivirira muviri uye masoja ekudzivirira muviri: kune dziviriro itsva uye kurapwa
Pamusoro pemishonga, tekinoroji yezvekurapa iri kutungamira nzira dzinoshandiswa kudzivirira zvirwere, dzakadai sekugadzira majekiseni nema antibodies e monoclonal. Chimwe chinhu chikuru ndechekudzivirira zvakanyanya ma antibodies (bNAbs), ma antibodies anogona kudzivirira marudzi akawanda eHIV. Ma bNAbs ari kudzidzwa kudzivirira (passive prophylaxis) uye sechikamu chemaitiro ekurapa akabatanidzwa.
Tekinoroji yekugadzira ma antibodies inobvumira ma antibodies kuti agare kwenguva refu, kudzivirira hutachiona kwakasimba, kana kugona kuunganidza masero emuviri kuti aparadze masero ane hutachiona. Maitiro ekuongorora immune system akadai se flow cytometry uye single-cell sequencing anobatsira kuona mhinduro dzinoshanda dzeimmune system uye kunzwisisa kuti nei HIV ichinetsa kudzora immune system.
6. Kugadziriswa kwemajini uye nzira dze "kurapa"
Chimwe chezvinetso zvikuru neHIV kuvapo kwenzvimbo inochengeterwa utachiona: hutachiona hunogona "kuvanda" mune mamwe masero uye husingaite kuzvara, zvichiita kuti zviomere kushandisa maARV. Kana kurapwa kwamiswa, hutachiona hunogona kubuda zvakare. Saka, kutsvaga mushonga kunotarisa pakubvisa kana kudzora nzvimbo iyi.
Tekinoroji yekugadzirisa majini seCRISPR-Cas imwe yenzira dzinonakidza. Tsvagiridzo iri kuongorora kubatanidzwa kweHIV proviral DNA mumajini evanhu, akadai seCCR5, iyo receptor inoshandiswa neHIV kupinda mumasero. Kunze kweCRISPR, kunewo matekinoroji ekurapa akavakirwa paRNA uye "kick and kill" (activation latent virus and then kill cells) uye "block and lock" (kicking and lock" (kick and kill) kuti irambe yakavanzika zvachose).
Kunyange zvazvo ichivimbisa, tekinoroji iyi inosangana nematambudziko makuru: kuchengetedzeka, kunyatsorongeka kwekutarisa, njodzi yemigumisiro isiri iyo, uye kuoma kwekuisa sisitimu yekugadzirisa kune chaiyo tissue.
7. Miedzo yekiriniki uye kuongororwa kunotungamirirwa nedata
Tekinoroji yezvekurapa iri kushandurawo maitiro ekuyedza kwekiriniki. Nzira dzekutarisa huwandu hwehutachiona, zviratidzo zvemuviri, uye kuongorora kusapindirana nemishonga zviri kubatsira vaongorori kuongorora kushanda kwezvirongwa panguva chaiyo. Uyezve, big data nehunyanzvi hwekugadzira zviri kushandiswa kuona maitiro emhinduro yekurapa, kufanotaura njodzi yekukundikana kwekurapwa, uye kugadzira nzira dzekudzivirira dzinoshanda zvakanyanya mumapoka akati wandei.
Kubatanidza ruzivo rwekiriniki, majini, uye maitiro kunogona kuwedzera kunzwisisa kwezvinhu zvinopesvedzera kubudirira kwekurapwa, kusanganisira kutevedzera mitemo, kudyidzana kwemishonga, uye zvimwe zvirwere zvakaita seTB kana hepatitis.
Mhedziso
Tekinoroji dzezvekurapa dzakachinja zvakanyanya mamiriro ekutsvagisa kweHIV. Kubva pakuongororwa nekukurumidza kweantigen nePCR, kusvika pakurongwa kwemajini ehutachiona kuburikidza neNGS, kusvika pakugadzirwa kwemishonga kuburikidza neHTS uye dhizaini yakavakirwa pachimiro, kusvika kuzvinhu zvitsva zvekudzivirira muviri zvakaita sebNAbs uye kuongorora majini ekuongorora - zvese zvakabatsira mukuvandudza zvakanyanya kudzora HIV zvichienzaniswa nemakumi emakore apfuura. Kunyange hazvo matambudziko akadai sekuchengetedza kwakavanzika uye kuramba mishonga zvichiripo, gwara rekutsvagisa riri kuwedzera kujeka: mishonga iri nyore kushandisa, kudzivirira kwakasimba, uye nzira dzekuwana mamiriro ekugara asina hutachiona. Mune ramangwana, kufambira mberi mune tekinoroji yezvekurapa kucharamba kuri kiyi yekufambisa nyika pedyo nechinangwa chekugumisa denda reHIV.
