Ukusebenzisa izakhi zofuzo njengomuthi: lona umqondo wokwelapha ngofuzo. Isu lokwelapha elihlanganisa ukuguqula izakhi zofuzo ukuze zelaphe isifo, ukwelapha ngezakhi zofuzo kusaqalwa kodwa imiphumela yakhona yokuqala iyethembisa.

Incazelo yokwelashwa kofuzo

Ukwelashwa ngofuzo kuhilela ukuguqula izakhi zofuzo ukuze kuvinjelwe noma ukwelapha izifo. Isekelwe ekudluliseleni isakhi sofuzo sokwelapha noma ikhophi yofuzo olusebenzayo kumaseli athile, ngenhloso yokulungisa iphutha lofuzo.

Izimiso eziyinhloko zokwelashwa kofuzo

Umuntu ngamunye wakhiwe ngamangqamuzana angaba yizigidi eziyizinkulungwane ezingama-70. Iseli ngalinye linamabhangqa angama-000 ama-chromosomes, akhiwe ngentambo emise okwe-helix, iDNA (deoxyribonucleic acid). I-DNA ihlukaniswe yaba izingxenye eziyizinkulungwane ezimbalwa, izakhi zofuzo, lapho sithwala khona amakhophi angama-23. Lezi zofuzo zakha ufuzo, ifa eliyingqayizivele lofuzo oludluliselwa ngabazali bobabili, eliqukethe lonke ulwazi oludingekayo ekukhuleni nasekusebenzeni komzimba. Izakhi zofuzo ngempela zibonisa indima yazo engqamuzaneni ngalinye entweni ephilayo.

Lolu lwazi lulethwa ngenxa yekhodi, inhlanganisela eyingqayizivele yezisekelo ezine-nitrogenous (adenine, thymine, cytosine kanye neguanine) ezakha iDNA. Ngekhodi, i-DNA yenza i-RNA, isithunywa esiqukethe lonke ulwazi oludingekayo (olubizwa ngokuthi ama-exons) ukuze kukhiqizwe amaprotheni, ngalinye elizodlala indima ethile emzimbeni. Ngaleyo ndlela sikhiqiza amashumi ezinkulungwane zamaprotheni abalulekile ekusebenzeni komzimba wethu.

Ukuguqulwa ngokulandelana kofuzo ngakho-ke kuguqula ukukhiqizwa kweprotheni, engasakwazi ukudlala indima yayo ngokufanele. Ngokuya ngezakhi zofuzo ezithintekayo, lokhu kungaholela ezinhlobonhlobo zezifo: umdlavuza, i-myopathies, i-cystic fibrosis, njll.

Umgomo wokwelashwa ngakho-ke ukuhlinzeka, ngenxa yohlobo lokwelapha, ikhodi efanele ukuze amaseli akhiqize amaprotheni entulekayo. Le ndlela yezakhi zofuzo iqala ngokubandakanya ukwazi kahle izindlela zesifo, ufuzo oluthintekayo kanye nendima yeprotheyini elisibekela yona.

Ucwaningo lwe-Gene therapy lugxile ezifweni eziningi:

• umdlavuza (65% wocwaningo lwamanje) 
• izifo ze-monogenic, okungukuthi izifo ezithinta isakhi esisodwa kuphela (i-hemophilia B, thalassemia) 
• izifo ezithathelwanayo (HIV) 
• isifo senhliziyo 
• izifo ze-neurodeergenerative (isifo sikaParkinson, isifo i-Alzheimer's, i-adrenoleukodystrophy, isifo sikaSanfilippo)
• izifo zesikhumba (i-junctional epidermolysis bullosa, i-dystrophic epidermolysis bullosa)
• izifo zamehlo (i-glaucoma) 
• njll

Iningi lezi zivivinyo zisasesicwaningweni sesigaba I noma sesi-II, kepha ezinye sezivele ziholele ekukhangisweni kwezidakamizwa. Lokhu kubandakanya:

• I-Imlygic, i-oncolytic immunotherapy yokuqala ngokumelene ne-melanoma, eyathola Ukugunyazwa kwayo Kwezokumaketha (Ukugunyazwa Kwezokuthengisa) ngo-2015. Isebenzisa igciwane le-herpes simplex-1 eliguquliwe ukuze lithelele amangqamuzana omdlavuza.
• I-Strimvelis, ukwelashwa kokuqala okususelwa kuma-stem cell, ithole Ukugunyazwa Kwezokumaketha ngo-2016. Yenzelwe izingane ezihlushwa yi-alymphocytosis, isifo esingajwayelekile semizimba yezakhi zofuzo ("bubble baby" syndrome)
• isidakamizwa i-Yescarta sikhonjiswe ekwelapheni izinhlobo ezimbili ze-non-Hodgkin lymphoma enolaka: i-B-cell lymphoma enkulu (LDGCB) kanye ne-refractory noma ebuyelwe kabusha eyinhloko ye-B-cell lymphoma enkulu ye-mediastinal (LMPGCB). Ithole ukugunyazwa kwayo kokumaketha ngo-2018.

Izindlela ezahlukahlukene zikhona ekwelashweni kofuzo:

• ukushintshwa kofuzo olunesifo, ngokungenisa ikhophi yofuzo olusebenzayo noma “ufuzo lokwelapha” kuseli eliqondiwe. Lokhu kungenziwa noma ku-vivo: isakhi sokwelashwa sijojelwa ngqo emzimbeni wesiguli. Noma ku-in vitro: ama-stem cells athathwa entanjeni yomgogodla, aguqulwa elebhu bese abuyiselwa esigulini.
• ukuhlela genomic kuqukethe ukulungisa ngqo ukuguquka kwezakhi zofuzo esitokisini. Ama-enzyme, abizwa ngokuthi ama-nucleases, azosika isakhi sofuzo endaweni lapho kuguqulwa khona izakhi zofuzo, bese kuba yingxenye ye-DNA bese ikwenza kube lula ukulungisa isakhi esishintshiwe. Nokho, le ndlela iseyiyokuhlola kuphela.
• ukuguqula i-RNA, ukuze iseli likhiqize iprotheni esebenzayo.
• ukusetshenziswa kwamagciwane aguquliwe, abizwa ngokuthi ama-oncolytics, ukubulala amangqamuzana omdlavuza.

Ukuze kufakwe isakhi sofuzo emangqamuzaneni esiguli, ukwelapha ngezakhi zofuzo kusebenzisa lokho okubizwa ngokuthi ama-vector. Imvamisa ziyizithwala magciwane, amandla anobuthi akhanseliwe. Abaphenyi njengamanje basebenza ekwakhiweni kwama-vectors angenagciwane.

Kwakungama-1950s, ngenxa yolwazi olungcono ngofuzo lomuntu, lapho umqondo wokwelashwa kofuzo wazalwa. Nokho, kuthathe amashumi ambalwa eminyaka ukuthola imiphumela yokuqala, esikweleta abacwaningi baseFrance. Ngo-1999, u-Alain Fischer nethimba lakhe e-Inserm bakwazile ukwelapha "amagwebu ezingane" aphethwe yisifo sokuqina komzimba esihlangene esixhunyaniswe ne-X chromosome (DICS-X). Iqembu seliphumelele impela ukufaka ikhophi ejwayelekile yesakhi esishintshiwe emzimbeni wezingane ezigulayo, kusetshenziswa i-vector yegciwane le-retrovirus yohlobo.