Application of Herpesvirus Saimiri as an Alternative Gene Therapy Vector

Year 2016, Volume: 25 Issue: 1, 41 - 51, 31.03.2016

Tuna Toptan

Abstract

Herpesvirus saimiri is the prototype rhadinovirus and is closely related to human Kaposi’s sarcoma-associated herpesvirus. Herpesvirus saimiri strains of subgroup C transduce a broad spectrum of cancer cells and primary cells including human T lymphocytes very efficiently and enable stable transgene expression. Herpesvirus saimiri as a gene therapy vector is favorable because of its large packaging capacity, extensive cell tropism, and long-termed persistence as non-integrating episomes and thus exhibits numerous advantages over commonly used viral vectors. In order to use Herpesvirus saimiri as a secure and versatile gene therapy vehicle, it should be easily manipulated and modified. The recent advances in molecular cloning of large genomic fragments such as virus genomes as bacterial artificial chromosomes facilitated the functional studies and manipulation of herpesviruses using the recombination system of bacteria. Among these, red-recombination based “en passant” mutagenesis method enables seamless genome modification such as deletion, insertion and point mutation very easily and efficiently.

Keywords

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Herpesvirüs Saimiri’nin Alternatif Gen Terapi Vektörü Olarak Kullanımı

Abstract

Herpesvirüs saimiri, gama herpesvirüs ailesine ait olan radinovirüslerin prototipidir ve insan Kaposi Sarkom-ilişkili herpesvirüs ile benzerlik gösterir. Herpesvirüs saimiri’nin C türü insan T lenfositleri olmak üzere birçok normal ve kanser hücre tipini yüksek verimlilikte transdükte etme ve bu hücrelerde sabit transgen ekspresyonu sağlamaktadır. Herpesvirüs saimiri, büyük transgen taşıma kapasitesi, geniş hücre tropizmi ve konak genomuna entegre olmadan epizomal olarak persiste olabilmesi özelliklerinden dolayı genterapisi için sıkça kullanılan viral vektörlere karşı üstünlük gösterir. Herpesvirüs saimiri’nin gen terapi vektörü olarak kullanımını sağlamak için güvenilir ve kolay bir şekilde manipüle edilebilmesi gerekir. Son 20 yılda birçok herpesvirüs  genomu bakteri yapay kromozomları olarak klonlanmıştır. Bu sayede viral genomlar, bakterilerin rekombinasyon sistemi kullanılarak modifiye edilebilmektedir. Bu yöntemlerden red-rekombinasyon temelli “en passant” mutagenez yöntemiyle herpesvirüslerde genomik delesyon, insersiyon ve nokta mutasyonlar geride hiçbir iz bırakmadan kolayca ve verimli bir şekilde yapılabilmektedir.

Keywords

Herpesvirüs saimiri, viral vektörler, gen terapi, rekombinasyon

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• Correspondence Address / Yazışma Adresi Tuna Toptan
• University of Pittsburgh Cancer Institute
• Cancer Virology Program Pittsburgh, PA, USA
• e-mail: [e-mail]
• Geliş tarihi/ Received: 11.05.2015
• Kabul tarihi/Accepted: 02.06.2015