RNA tabanlı nükleaz sistemi olan CRISPR (clustered regularly interspaced short palindromic repeats) temelli genom düzenleme teknolojisi, bakterilerin plazmit veya nükleik asit içeren viral kapsidlere karşı geliştirdiği direnç mekanizmalarından biridir. CRISPR/Cas sistemi yabancı DNA'ya ait küçük DNA parçalarının prokaryotik hücrenin genomuna katılmasını sağlar. Böylece konakçı hücrenin aynı istilacı ile yeniden karşılaşması durumunda, adaptif bağışık yanıt devreye girer. CRISPR/Cas sistemi çeşitli viral vektörler ve lipid partiküller gibi taşıyıcı sistemler ile biyolojik ortamlara uygulanarak hücrelerin genomunda değişiklik yapılmasını sağlar. Bu nedenle CRISPR/Cas sistemi beta talasemi, orak hücreli anemi, duchenne kas distrofisi, transtiretin amiloidosis ve Leber konjenital amorozisi gibi hastalıklarda genomda mutasyondan etkilenen bölgeyi düzeltmek amacıyla kanser gibi hastalıklarda ise terapötik strateji olarak preklinik ve klinik çalışmalarda değerlendirilmektedir. Makalede CRISPR/Cas sistemi açıklanarak; literatürde bu sistemin biyolojik ortamlara uygulandığı, genetik hastalıklar ve kanser gibi çeşitli klinik durumların tedavisinde etkinliği ve güvenilirliğinin değerlendirildiği araştırmaların sonuçları sistematik şekilde derlenerek sunulmuştur.
Anahtar Kelimeler: CRISPR/Cas sistem; taşıyıcı sistemler; pre-klinik/klinik çalışmalar
CRISPR (clustered regularly interspaced short palindromic repeats)-based genome technology, which is an RNA-based nuclease system, is one of the resistance mechanisms developed by bacteria against viral capsids containing plasmid or nucleic acid. The CRISPR/Cas system provides that small DNA fragments of foreign DNA to be integrated into the genome of the prokaryotic cell and the adaptive immune response is activated when the host cell encounters the same invader again. The CRISPR/Cas system can be applied to biological systems with various vehicle systems such as viral vectors and lipid particles, allowing modifications to the genome of cellThus, in the event that the host cell encounters the same invader again, the adaptive immune response is activated. Furthermore, in order to correct the region affected by mutation in the genome in diseases such as beta thalassemia, sickle cell anemia, duchenne muscular dystrophy, transthyretin amyloidosis and leber congenital amorosis and also in cancer, CRISPR system is evaluated in preclinical and clinical studies as a therapeutic strategy. In this article, by explaining the CRISPR/Cas system, it was reviewed and presented the results of the studies in which this system was applied to biological environments and the effectiveness and safety of the treatment of various clinical conditions such as genetic diseases and cancer in the literature.
Keywords: CRISPR/Cas systems; vehicle systems; preclinical and clinical studies
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