CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved
CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved
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DOI：
10.1089/108729001753231713
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发表时间：
2001-10-01
期刊：
影响因子：
--
通讯作者：
van den Hurk, LV
中科院分区：
文献类型：
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作者：
Rankin, R;Pontarollo, R;van den Hurk, LV
含有CpG基序的寡核苷酸在体外刺激脊椎动物免疫细胞，在小鼠疾病模型中已被证明有效，目前正在人体临床试验中作为癌症、过敏和传染病的治疗方法进行测试。由于没有已知的兽医物种的免疫刺激基序，CpG DNA作为兽药的潜力尚未被研究。在这里，最佳的CpG基序为七个兽医和三个实验室物种描述。GTCGTT基序的优先识别在两个脊椎动物门中是强烈保守的，尽管GACGTT基序在小鼠和兔子的近交系中是最佳的。在随后的佐剂性试验中，体外筛选方法在绵羊中得到验证，这是首次在兽医物种中证明CpG DNA的有效性。这些结果将为兽医提供候选免疫刺激剂和治疗药物，并使CpG DNA能够在人类疾病的大型动物模型中进行测试。
Oligodinucleotides containing CpG motifs stimulate vertebrate immune cells in vitro, have proven efficacy in murine disease models and are currently being tested in human clinical trials as therapies for cancer, allergy, and infectious disease. As there are no known immunostimulatory motifs for veterinary species, the potential of CpG DNA as a veterinary pharmaceutical has not been investigated. Here, optimal CpG motifs for seven veterinary and three laboratory species are described. The preferential recognition of a GTCGTT motif was strongly conserved across two vertebrate phyla, although a GACGTT motif was optimal for inbred strains of mice and rabbits. In a subsequent adjuvanticity trial, the in vitro screening methodology was validated in sheep, representing the first demonstration of CpG DNA efficacy in a veterinary species. These results should provide candidate immunostimulant and therapeutic drugs for veterinary use and enable the testing of CpG DNA in large animal models of human disease.