Exploring the catalytic and electronic potential of DNA and RNA

我建议深入研究DNA和RNA这两种令人意想不到的化学催化特性，它们是所有生物的遗传物质。这些特性是在我的实验室中发现的，并证明了由RNA/DNA制成的酶能够(A)利用光能催化光化学反应(在我们的案例中，修复嘧啶二聚体-DNA本身中由紫外线产生的损伤)；以及(B)结合一种普遍存在的细胞辅因子--血红素--并利用它催化一些在活细胞中通过利用血红素的蛋白质酶进行的氧化化学反应。RNA和DNA，名义上是携带信息的生物聚合物，能够复制高度专门化蛋白质的这些特殊催化活性，这一事实具有广泛的影响。这些包括原始进化中的RNA酶进行类似活动的可能性；它们也为我们提供了一个独特的一瞥，即如何从非蛋白质聚合物中构建酶。最有趣的是，我们的DNAzyme比它们的蛋白质同行更小、更便宜、更坚固，正被证明是在世界各地具有重要实用价值的试剂，用于生物传感和组织化学应用。

I propose to investigate in depth two highly unexpected chemical catalytic properties of DNA and RNA, the genetic material of all living organisms. These properties were discovered in my laboratory, and demonstrate that enzymes made out of RNA/DNA are able to (a) harness the energy of light to catalyze photochemical reactions (in our case, the repair of pyrimidine dimers-- UV light-generated lesions in DNA itself); and (b) bind a ubiquitous cellular cofactor-- heme-- and utilize it to catalyze some of the same oxidative chemistries that are carried out in living cells by heme-utilizing protein enzymes. The fact that RNA and DNA, nominally information-carrying biopolymers, are able to replicate these particular catalytic activities of highly specialized proteins has wide ramifications. These include the possibility that RNA enzymes in primordial evolution carried out similar activities; they also provide us with a unique glimpse of how enzymes can be built from non-protein polymers. Most interestingly, our DNAzymes, which are smaller, cheaper, and more robust than their protein counterparts, are turning out to be reagents of significant practical utility worldwide, for biosensing and histochemical applications.