Marvin H. Caruthers
Distinguished Professor

Office: JSCBB B420
Lab: JSCBB D251


PhD: Northwestern University, 1968
Postdoctoral Fellow: University of Wisconsin, 1968-1970 

Areas of Expertise

Bio-Analytical Chemistry, Bio-Inorganic Chemistry, Gene Expression and Regulation, Genetics and Chemical Biology, and Nucleic Acids.

Awards and Honors

  • 2023 Merkin Prize
  • 2018 Elected American Association Advancement of Science Fellow
  • 2018 Elected to National Academy of Inventors
  • 2018 Elected to National Inventors Hall of Fame
  • 2018 Oligonucleotide Therapeutic Society Lifetime Achievement Award
  • 2015 Elected as a Corresponding Member of the Academy of Sciences Göttingen, Germany
  • 2014 ACS Award for Creative Invention
  • 2014 Frantisek Sorm Medal, Academy of Sciences of the Czech Republic 
  • 2014 National Academy of Science Award in Chemical Sciences
  • 2012 The Biotech Meeting 25th Anniversary Hall of Fame Recognition Award, Laguna Beach CA
  • 2010 Boulder County Business Hall of Fame Award
  • 2009 Girindus Leadership in Oligonucleotides Award
  • 2009 Icon of Boulder Award
  • 2009 Iowa State University Distinguished Alumnus Award
  • 2008 Robert Stearns Award for Extraordinary Contributions to the University of Colorado 
  • 2006 American Society for Microbiology The Promega Biotechnology Research Award
  • 2006 The Economist Innovation Award, London, England
  • 2006 Imbach-Townsend Award of the International Society of Nucleic Acid Research 
  • 2006 International Society of Nucleic Acids Research Imbach-Townsend Award
  • 2006 National Medal of Science, Washington, D.C.
  • 2005 National Academy of Sciences in Chemistry for Service to Society Award
  • 2004 Prelog Medal in Recognition of Pioneering Work on the Chemical Synthesis, Zurich, Switzerland  
  • 1999 ABRF — Hewlett Packard Award for Outstanding Contributions to Biomolecular Technologies  
  • 1996 Alumni Merit Award, Northwestern University
  • 1996 Doctor of Science Honorary Degree, University of Nebraska 
  • 1995 Bonfils-Stanton Award for Science
  • 1994 American Academy of Arts & Sciences Elected Member
  • 1994 Elliott Cresson Medal of the Franklin Institute
  • 1994 National Academy of Sciences Elected Member
  • 1992 International Biotechnology Ventures Award
  • 1984-1985 CRCW Faculty Research Lectureship, University of Colorado 
  • 1981 Guggenheim Fellow
  • 1975-1980 USPHS Career Development Award

Nucleic Acid Chemistry and Biochemistry

Professor Caruthers’ laboratory has also pioneered the synthesis of many new nucleic acid analogues that have found applications in the nucleic acid diagnostic and therapeutic areas. Two of these analogues will be discussed.

1.) Phosphonoacetate Oligonucleotides and the Crispr/Cas System.

Several years past we developed methodologies leading to the chemical synthesis of oligonucleotides having phosphonoacetate internucleotide linkages [Solid Phase Chemical Synthesis of Phosphonoacetate and Thiophosphonoacetate Oligodeoxynucleotides. D. J. Dellinger, D. M. Sheehan, N. Christensen, J. G. Lindberg and M. H. Caruthers. J. Am. Chem. Soc. 125, 940 (2003)] and the development of this synthesis strategy was quickly followed by a series of biological and biochemical studies of these phosphonoacetate and thiophosphonoacetate analogues [Biochemical Properties of Phosphonoacetate and Thiophosphonoacetate Oligodeoxynucleotides. D. M. Sheehan, B. Lunstad, C. M Yamada, B. Stell, M. H. Caruthers and D. J. Dellinger, Nucleic Acids Res. 31, 4109 (2003)]. Recently the effects of various chemical modifications in guide RNAs (gRNAs) at defined positions and combinations have been investigated (Phosphonoacetate Modifications Enhance the Stability and Editing Yields of Guide RNAs for Cas9 Editors. Daniel E. Ryan, Tamar Diamant-Levi, Israel Steinfeld, David Taussig, Savita Visal-Shah, Suhani Thakker, Benjamin D. Lunstad, Robert J. Kaiser, Ryan McCaffrey, Michael Ortiz, Justin Townsend, William R. W. Welch, Mandeep Singh, Bo Curry, Douglas J. Dellinger, and Laurakay Bruhn.]. These investigators found that 2′-O-methyl-3′- phosphonoacetate (MP) modifications were substantially more effective than 2′-O-methyl-3′-phosphorothioate (MS) modifications at the 3′ ends of single-guide RNAs (sgRNAs) towards promoting high editing yields, in some instances an order of magnitude higher in human cells

2.) Thiomorpholino Oligonucleotides.

a.In 2020 the Caruthers’ Laboratory published the synthesis of thiomorpholino oligonucleotides, TMOs, (Synthesis and Characterization of Thiophosphoramidate Morpholino Oligonucleotides and Chimeras. H. Langner, K. Jastrzebska, and M. H. Caruthers. J. Am. Chem. Soc.142, 16240 (2020). During the past two years we have significantly improved the chemistry and can now prepare very pure TMOs at the 200-mg level, which is sufficient for all the cell biology and mouse studies that we currently contemplate. We have published our initial research using TMOs to block intron excision in TUG1 and TERT RNAs (Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention. G. Dumbović, U. Braunschweig, H. Langner, M. Smallegan, J. Biayna, E. P. Has, K. Jastrzebska, B. Blencowe, T. R. Cech, M. H. Caruthers & J. L. Rinn. Nature Communications 12, 3308 (2021). More recently we have published our initial exon skipping results in the mdx mouse model for DMD (Thiomorpholino oligonucleotides as a robust class of next generation platforms for alternate mRNA splicing. B. T. Lea, S. Paul, K. Jastrzebska, H. Langer, M. H. Caruthers, and R. N. Veedu. PNAS 2022 Vol. 119 No. 36 e2207956119. Currently underway with many different collaborators are biological studies focused on the use of this analogue as a therapeutic drug for the treatment of various genetic diseases (listed below).

See my NCBI bibliography for a full and up-to-date list

  • Synthesis and Charactization of Thiophosphoramidate Morpholino Oligonucleotides and Chimeras. H. Langer, K. Jastrzebska, and M. H. Caruthers. J. Am. Chem. Soc. 142, 16240 (2020).
  • DNA Analogues Modified at the Nonlinking Positions of Phosphorus. P. Kumar, and M. H. Caruthers. Accts. Chem. Res. 53, 2152 (2020).
  • Nuclear Compartmentalization of TERT mRNA and TUG1 lncRNA Is Driven by Intron Retention. G. Dumbović, U. Braunschweig, H. Langner, M. Smallegan, J. Biayna, E. Hass, K. Jastrzebska, B. Blencowe, T. Cech, M. H. Caruthers, & J. Rinn. Nature Communications (2021) 12:3308.
  • Thiomorpholino Oligonucleotides as a Robust Class of Next Generation Platforms for Alternate mRNA Splicing. B. T. Lea, S. Paul, K. Jastrzebska, H. Langer, M. H. Caruthers, and R. N. Veedu.Proceedings National Academy of Science (2022) 119:7956.