Kushandisa majini semushonga: iyi ndiyo pfungwa yekuseri kwejene kurapwa. Therapeutic strategy inosanganisira kugadzirisa majini kurapa chirwere, gene therapy ichiri muhucheche asi mhedzisiro yayo yekutanga iri kuvimbisa.

Tsanangudzo yekurapa kwemajini

Kurapa kweGene kunosanganisira kushandura masero kudzivirira kana kurapa chirwere. Inobva pakuendeswa kwejene rekurapa kana kopi yejini rinoshanda mumasero chaiwo, nechinangwa chekugadzirisa kukanganisa kwemajini.

Misimboti mikuru ye gene therapy

Munhu mumwe nomumwe akaumbwa nemasero anosvika mabhiriyoni makumi manomwe. Sero rimwe nerimwe rine mapeya 70 emachromosome, akaumbwa nekaviri kaviri helix-shaped filament, DNA (deoxyribonucleic acid). DNA yakakamurwa kuita zviuru zvishoma zvikamu, majini, ayo isu tinotakura makopi makumi maviri nematatu. Aya majini anoumba genome, yakasarudzika nhaka yekuzvarwa inofambiswa nevabereki vese, iyo ine ruzivo rwese rwunodiwa mukusimudzira nekushanda kwemuviri. Majini acho anoratidza sero rimwe nerimwe basa raro muchinhu chipenyu.

Ruzivo urwu rwunopihwa nekuda kwekodhi, musanganiswa wakasiyana we4 nitrogenous base (adenine, thymine, cytosine uye guanine) inoumba DNA. Nekodhi, DNA inogadzira RNA, mutumwa ane ruzivo rwese rwunodiwa (inonzi maexons) kugadzira mapuroteni, rimwe nerimwe rine basa chairo mumuviri. Nokudaro tinogadzira makumi ezviuru zvemapuroteni anokosha pakushanda kwemuviri wedu.

Kugadziriswa mukutevedzana kwejeni saka kunoshandura kugadzirwa kweprotein, iyo isingachakwanise kutamba basa rayo nemazvo. Zvichienderana nejini rinobatanidzwa, izvi zvinogona kukonzera zvirwere zvakasiyana-siyana: kenza, myopathies, cystic fibrosis, nezvimwewo.

Nheyo yekurapa ndeyekupa, nekuda kwejini rekurapa, kodhi chaiyo kuitira kuti masero agone kuburitsa protein inoshaikwa. Iyi nzira yejini yekutanga inosanganisira kuziva chaizvo maitiro echirwere, geni rinobatanidzwa uye basa reprotein iro rinonyora.

Gene therapy research inotarisa pazvirwere zvakawanda:

• kenza (65% yetsvagiridzo yazvino) 
• monogenic zvirwere, kureva zvirwere zvinongobata geni rimwe chete (hemophilia B, thalassemia) 
• zvirwere zvinotapukira (HIV) 
• Chinetso chepfungwa 
• neurodegenerative zvirwere (chirwere cheParkinson, chirwere cheAlzheimer, adrenoleukodystrophy, chirwere cheSanfilippo)
• dermatological zvirwere (junctional epidermolysis bullosa, dystrophic epidermolysis bullosa)
• zvirwere zvemaziso (glaucoma) 
• etc.

Mazhinji emiedzo achiri muchikamu chekutanga kana chechipiri chekutsvagisa, asi zvimwe zvakatokonzera kutengeswa kwemishonga. Izvi zvinosanganisira:

• Imlygic, yekutanga oncolytic immunotherapy inopesana nemelanoma, iyo yakagamuchira Mvumo yeKushambadzira (Marketing Authorization) muna 2015. Inoshandisa genetically modified herpes simplex-1 utachiona kuti iparadze masero ekenza.
• Strimvelis, the first therapy based on stem cells, yakawana Marketing Authorization muna 2016. Yakagadzirirwa vana vanotambura nealymphocytosis, isingawanzowanikwi genetic immune disease ("bubble baby" syndrome)
• mushonga weYescarta unoratidzwa pakurapa kwemhando mbiri dzehasha dzisiri Hodgkin lymphoma: diffuse hombe B-cell lymphoma (LDGCB) uye refractory kana kudzoreredza chepakutanga mediastinal hombe B-cell lymphoma (LMPGCB). Yakagamuchira Mvumo yeKushambadzira muna 2018.

Kune nzira dzakasiyana siyana mukurapa kwejeni:

• kutsiviwa kwejini rine chirwere, nokupinza kopi yejini rinoshanda kana kuti “gene rekurapa” musero rinotarirwa. Izvi zvinogona kuitwa chero muvivo: iyo gene yekurapa inobaiwa yakananga mumuviri wemurwere. Kana kuti in vitro: stem masero anotorwa kubva kumusana, anogadziridzwa murabhoritari uye anodzoserwa mumurwere.
• genomic editing inosanganisira kugadzirisa zvakananga genetic mutation muchitokisi. Ma Enzymes, anonzi nucleases, anocheka jenasi panzvimbo yekuchinja kwaro, ipapo chikamu cheDNA chinobva chaita kuti zvikwanise kugadzirisa gene rakashandurwa. Zvisinei, nzira iyi ichiri kungoedza chete.
• kugadzirisa RNA, kuitira kuti sero ribudise puroteni inoshanda.
• kushandiswa kwemavhairasi akagadziridzwa, anonzi oncolytics, kuuraya cancer maseru.

Kupinza jena rekurapa mumasero omurwere, kurapwa kwemajini kunoshandisa anonzi mavector. Vanowanzova mavhairasi mavhairasi, iyo ine chepfu inogona kubviswa. Vatsvagiri parizvino vari kushanda pakuvandudza mavhairasi asiri mavhairasi.

Makanga muri muma1950, nokuda kweruzivo rwuri nani rwejenome romunhu, apo pfungwa yokurapa magene yakavapo. Nekudaro, zvakatora makumi emakore akati wandei kuti tiwane mhedzisiro yekutanga, yatinayo kune vaongorori veFrance. Muna 1999, Alain Fischer nechikwata chake kuInserm vakakwanisa kurapa “mucheche mabubbles” airwara nekusakwana kwemuviri kwakabatana neX chromosome (DICS-X). Chikwata chakanyatsobudirira kuisa kopi yakajairwa yejini rakachinjwa mumuviri wevana vanorwara, vachishandisa retrovirus-mhando yehutachiona hwehutachiona.