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Hachimoji DNA and RNA: A genetic system with eight building blocks

Shuichi Hoshika, Nicole A. Leal, Myong‐Jung Kim, Myong‐Sang Kim, Nilesh B. Karalkar, Hyo‐Joong Kim, Alison M. Bates, Norman E. Watkins, Holly A. SantaLucia, Adam J. Meyer, Saurja DasGupta, Joseph A. Piccirilli, Andrew D. Ellington, John SantaLucia, Millie M. Georgiadis, Steven A. Benner

📄 Abstract

We report DNA- and RNA-like systems built from eight nucleotide “letters” (hence the name “hachimoji”) that form four orthogonal pairs. These synthetic systems meet the structural requirements needed to support Darwinian evolution, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to increase the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos.

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