2. Academic Validation
  3. Hachimoji DNA and RNA: A genetic system with eight building blocks

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

  • Science. 2019 Feb 22;363(6429):884-887. doi: 10.1126/science.aat0971.
Shuichi Hoshika 1 2,  Nicole A Leal 1 2,  Myong-Jung Kim 1 2,  Myong-Sang Kim 1,  Nilesh B Karalkar 1 2,  Hyo-Joong Kim 1,  Alison M Bates 3,  Norman E Watkins Jr 4,  Holly A SantaLucia 4,  Adam J Meyer 5,  Saurja DasGupta 6,  Joseph A Piccirilli 6,  Andrew D Ellington 5,  John SantaLucia Jr 4,  Millie M Georgiadis 3,  Steven A Benner 7 2
Affiliations

Affiliations

  • 1 Firebird Biomolecular Sciences LLC, 13709 Progress Boulevard, No. 17, Alachua, FL 32615, USA.
  • 2 Foundation for Applied Molecular Evolution, 13709 Progress Boulevard, No. 7, Alachua, FL 32615, USA.
  • 3 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • 4 DNA Software Inc., Ann Arbor, MI 48104, USA.
  • 5 Center for Systems and Synthetic Biology, University of Texas, Austin, TX 78703, USA.
  • 6 Department of Biochemistry and Molecular Biology and Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
  • 7 Firebird Biomolecular Sciences LLC, 13709 Progress Boulevard, No. 17, Alachua, FL 32615, USA. [email protected].
PMID: 30792304 DOI: 10.1126/science.aat0971
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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