Dong Wang from the University of California San Diego and Steven Benner of the Foundation for Applied Molecular Evolution in Alachua, Florida, have made remarkable advancements in synthetic biology by showing that Escherichia coli RNA polymerase can transcribe a DNA template featuring a synthetic letter nearly as effectively as a natural base pair. Their research was published on September 2, 2026, in Nature Communications, supported by gel assays and cryo-electron microscopy structures at high resolutions.<\/p>\n
The Hachimoji alphabet, which merges the four natural DNA bases with four synthetic ones, was first introduced by Benner and his team in 2019. This research specifically examines the synthetic pair P and Z, which, in contrast to the previously characterized B:S pair, had not been assessed in multi-subunit RNA polymerases present in cells.<\/p>\n
During their experiments, the researchers employed DNA and RNA scaffolds with a single unnatural base, assessing 32 combinations of templates and substrates. They discovered that the addition of the complementary synthetic partner (like PTP paired with dZ) generated an extension band within 15 seconds. Both single-turnover kinetics and chase experiments validated the polymerase’s capability to maintain transcription past the synthetic base pair.<\/p>\n
These studies were performed outside of living organisms, utilizing purified Escherichia coli RNA polymerase in controlled lab conditions. The importance of this research lies in confirming that the synthetic letters can pair consistently within the parameters of the Hachimoji system, broadening the potential uses of synthetic genetic information.<\/p>\n
The team recognized that a specific challenge with the P:Z pairing design involves the deprotonation of Z, resulting in GTP misincorporation. To tackle this issue, they created a Z analogue, Z*, which significantly decreases these misincorporation rates, although it does not entirely eliminate them.<\/p>\n
Finally, by utilizing an RNA aptamer strategy, Wang, Benner, and their colleagues envision applying their expanded genetic alphabet for practical uses such as targeting particular cancer cells, while noting that achieving operational cellular use of the eight-letter system is still to be realized.<\/p>\n","protected":false},"excerpt":{"rendered":"
Dong Wang from the University of California San Diego and Steven Benner of the Foundation for Applied Molecular Evolution in Alachua, Florida, have made remarkable advancements in synthetic biology by showing that Escherichia coli RNA polymerase can transcribe a DNA template featuring a synthetic letter nearly as effectively as a natural base pair. Their research […]<\/p>\n","protected":false},"author":2,"featured_media":375978,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"Default","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[179],"class_list":["post-375977","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-source-scienceblog-com"],"_links":{"self":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/posts\/375977","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=375977"}],"version-history":[{"count":0,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/posts\/375977\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/media\/375978"}],"wp:attachment":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=375977"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=375977"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=375977"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}