Novel Method for Reverse Automated Nucleic Acid Synthesis


Project ID:  D2017-49



Automated processes are widely used in the synthesis of modified oligonucleotide strands.  These modified oligonucleotides are useful in the treatment or investigation of various conditions and diseases. Currently, the most common subunits used to synthesize RNA strands in the 3 to 5 direction are 3 phosphoramidites. There remains a need for novel methods to facilitate RNA synthesis form the 5 to 3 position using H-phosphonate chemistry.


Invention Description

Researchers at the University of Toledo, led by Dr. Amanda Bryant-Friedrich, have developed a novel automated method to synthesize oligonucleotides, which reduces the number of required steps and also allows for more flexibility in in adding modifications to the sugar moiety. The method developed here relies novel activated monomers for polymer synthesis and takes advantage of existing standard protocols and reagents, which will allow easy integration into conventional protocols. This process that employs 5 H-phosphonate modified ribonucleotides to allow for the automated synthesis of modified RNA in the 5 to 3 direction. 



•       Tools for the investigation of biological processes

•       Synthesis of artificial genes

•       Antisense small oligonucleotides (snRNA)



•       The monomers and solid supports used in the synthesis are novel and unavailable commercially

•       The synthesis procedure uses less steps and is more economical than conventional methods

•       The synthesis method used results in enhanced chemical stability of the monomers

•       The method is amenable to the inclusion of sugar modifications

•       The synthesis method developed here is more environmentally friendly and based on well-established polymer synthesis chemistry

•       The method developed takes advantage of conventional protocols and reagents and can be easily incorporated into currently existing protocols for oligonucleotide synthesis



Bedi MF et al., Synthesis of damaged DNA containing the oxidative lesion 3’-oxothymidine. Bioorganic Medicinal Chemistry, 2017, 5598-5602


 Audat SA et al., Synthesis of C3’ modified nucleosides for selective generation of the C3’-deoxy-3’-thymidinyl radical: a proposed intermediate in LEE induced DNA damage. Journal of Organic Chemistry, 2012, 3829-3837


Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Reverse automated nucleic acid synthesis Utility United States 16/384,080 10,927,140 4/15/2019 2/23/2021 4/15/2039 Issued
For Information, Contact:
Stephen Snider
AVP Tech Transfer
The University of Toledo
419 530 6225
Amanda Bryant-Friedrich
Matthew Ellis
Nucleic acid