得一提的是，我們用毒液充當毒腺組織，結果在沒有 犧牲動物的情況下，我們從希拉毒蜥身上成功克隆 了exendin-4，同時也獲得了希拉毒蜥exendin-3的 首組基因數據。此外，我們也從墨西哥串珠蜥蜴身上 獲得了exendin-3 及其先導體的首組基因數據。我 們的結果證明，採用凍乾長達一年以上的原毒液，也 可以成功克隆互補脫氧核糖核酸（cDNA）。雖然這 些凍乾的原毒液樣本經過長期冷凍儲存，但我們仍然 能夠成功地將其毒液蛋白質的多聚腺苷酸信使核糖核 酸（polyadenylated mRNA）復原。而通過這種技術 得出的基因數據可用於科學研究與疾病治療。實驗中 我們還發現，正如原毒液所展示，培植具有兩親合成 縮氨酸的即時聚合酶鏈式反應（RT-PCR）產品會產 生滯留效應。我們的結論是，爬行類動物毒液的信使 核糖核酸(mRNA) 保護是通過目前尚不明確的成分來 實現的，而本實驗所採用的程序步驟有效地揭示了毒 液腺的轉錄組。以這項創新發現為基礎，我們進一步 從毒蜥毒液中分離出染色體脫氧核糖核酸（genomic DNA）。我們從墨西哥串珠蜥蜴凍乾的毒液中成功克 隆了全新的局部12S核糖體核糖核酸基因（partial 12S rRNA gene）。本研究是首次用爬行類動物毒液 的單個樣本證明樣本中不僅含有該動物的毒液腺蛋白 質組和轉錄組，而且亦含有該動物的基因組。這些發 現為獲取分子數據提供了一種快速、非致命性、非侵 入性的方法。這種方法不僅不會降低數據的科學穩健 性，而且還提供了對同一個瀕危標本開展並連續重複 研究的可能性。 基於毒液的縮氨酸發現方法已成為醫藥行業關注的領 域，目前很多生物技術公司已看到源自各種動物毒液 縮氨酸的巨大潛力，並開始思考如何從進化過程中所 產生的選擇性和敏感性（表1）裡尋找新的商機。《新 科學人》期刊最近發表的一份報告稱，毒液研究已進 入基因組時代；換言之，毒液研究已不再是過去那種 從成千上萬有毒物質中篩選出潛在藥物的費時費力 的工作，而是變成一個高通量的科研技術過程。也因 此，毒液不僅成為一個明顯藥源，更成為醫藥業最熱 的科研項目之一。 venom itself -- essentially using the venom as a surrogate venom gland tissue for this purpose. The process worked extremely well. We successfully cloned exendin-4 from Gila monster and also obtained the first genetic data on exendin-3 and their precursor from Mexican beaded lizard without sacrifice of endangered herprtofauna. We showed that successful cDNA cloning could be achieved from lyophilised venom stored in a freezer for more than a year. Despite each of these preparations having been either taken or stored under what would be considered to be sub-optimal conditions, polyadenylated mRNA for the venom proteins was recovered in a form that facilitated RT-PCR and the genetic data generated by this technique could be useful for scientific and therapeutic purposes. In our laboratory, we have also found that incubation of RT-PCR products with synthetic amphipathic peptides produces the gel retardation effect as demonstrated here with crude venom. We conclude that nucleic acid (mRNA) protection in reptile venom is afforded by such as yet unidentified components and that the procedure employed in this study effectively unmasks the transcriptome of the venom gland. Following from this original discovery, we extended these studies to isolate genomic DNA from the helodermatid venom. The novel partial 12S rRNA gene for Mexican beaded lizard was successfully cloned from its lyophilised venom. This study is the first reported where a single sample of reptile venom has been shown to contain the animal’s genome in addition to the venom gland proteome and transcriptome. Such findings offer a rapid, non-lethal and noninvasive approach to obtaining molecular data in a manner that does not compromise scientific robustness and that, additionally, offers the possibility of performing and serially-repeating such studies on the same individual endangered specimens. The field of venom-based peptide discovery approach is of interest to the pharmaceutical industry as a number of biotechnology companies have already recognised the enormous potential inherent in peptides derived from many different kinds of animal venom, and have begun to exploit the selectivity and sensitivity fine-tuned by evolution (Table 1). A recent report published in New Scientist claims that venom research has entered the genomics age, turning the once-laborious job of sifting through toxic cocktails for potential cures into a high-throughput process. As a result, venoms have become an obvious source of drugs and have become one of the hottest commodities in pharmaceuticals. UMAGAZINE ISSUE 10 64 學院專欄．FACULTY COLUMN
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