Technologia CRISPR-Cas9 jako potencjalna terapia mukowiscydozy
Słowa kluczowe:
CRISPR/Cas9, mukowiscydoza, Terapia genowaStreszczenie
Abstrakt
Mukowiscydoza (Cystic fibrosis – CF) jest jedną z najczęściej występujących śmiertelnych chorób genetycznych. Powikłania płucne CF warunkują 90% zgonów wśród pacjentów cierpiących na CF. Głównymi ograniczeniami aktualnych terapii CF jest brak skuteczności leków na wszystkie warianty mutacji CFTR. Przełomem w poszukiwaniu skuteczniejszego leczenia CF może okazać się edycja genów wykorzystująca CRISPR-Cas9. Technologia CRISPR-Cas9 dzięki swojej precyzyjności i efektywności edycji genów mogłaby przynieść znaczne poprawy skuteczności leczenia CF. W terapii CF z wykorzystaniem CRISPR-Cas9 możliwa jest korekcja mutacji w genie CFTR, co umożliwia nie tylko złagodzenie objawów, ale również korekcje przyczyny CF. Możliwości terapeutyczne CRISPR-Cas9 w terapii CF zostały udowodnione poprzez korekcje delecji F508 w jednojądrzastych komórkach krwi obwodowej. Przy wykorzystaniu CRISPR-Cas9 udało się przywrócić prawidłowe funkcjonowanie CFTR do 40.2%, 74%, 88% wartości prawidłowo funkcjonujących CFTR. Wykazano również częściowe przywrócenie prawidłowych funkcji CFTR wraz z równoległym obniżeniem aktywności nabłonkowych kanałów Na+ w rzadszych wariantach CF. Udowodniono możliwość dokonania edycji genów za pomocą CRISPR-Cas9 w warunkach in vivo. Aktualnie największym ograniczeniem CRISPR-Cas9 jest skuteczność dostarczania kompleksów CRISPR-Cas9 do komórek. Brakuje również danych na temat długofalowych skutków terapii CRISPR-Cas9 oraz mutacji off-target, co wymaga prowadzenia dalszych badań z wykorzystaniem technologii CRISPR-Cas9.
Słowa kluczowe: Mukowiscydoza, CRISPR-Cas9, Terapia genowa
Abstract:
Cystic fibrosis (CF) is one of the most common, lethal genetic disease in the world. Respiratory complications are leading cause of mortality in 90% of patient with CF. Main limitations in treatment of CF is lack of effective medication for all mutation variants. Breakthrough in finding effective treatment of CF may be gene editing using CRISPR-Cas9. Thanks to precision and efficiency CRISPR-Cas9 technology could increase effectiveness of CF treatment. In therapy of CF by using CRISPR-Cas9 possible is correcting mutation in CFTR gene, which not only can moderate symptoms but also correct the cause of the disease. Therapeutic applications of CRIPSR-Cas9 has been proven by correction of F508 deletion in peripheral blood mononuclear cells. By using CRIPSR-Cas9 restoration of functionality CFTR has been achieved in 40,2%, 74%, 88% in comparison with physiological CFTR. Partial restoration of CFTR functionality with simulations decreasing activity of epithelial Na+ canals has been achieved in more rare variants of CF. Gene editing applications of CRISPR-Cas9 has been proven on in vivo models. Currently the most prominent limitation of CRISPR-Cas9 is effective delivering CRISPR-Cas9 complexes to cells. There are no date regarding long-term results of CRISPR-Cas9 therapy or off-target mutations, which requires continuation of research using CRISPR-Cas9 technology.
Keywords: Cystic fibrosis, CRISPR-Cas9, Gene therapy
Bibliografia
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Opublikowane
24 sierpnia 2025
Prawa autorskie (c) 2025 Rafał Wąsek, Patrycja Maj, Anna Lis, Kazimierz Kukla
Licencja
Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa – Użycie niekomercyjne – Bez utworów zależnych 4.0 Międzynarodowe.
