Therapeutic Editing™

A Powerful Approach to Treating and Curing Diseases

ETAGEN’s Therapeutic Editing™ oligomers specifically bind to and permanently correct disease-causing mutations. ETAGEN employs proprietary chemically-modified nucleic acid oligomers (ETAMERS™) that act as both the guide and template for triggering precise editing by the endogenous DNA repair machinery, addressing the need for a more simple and specific editing platform for in vivo therapeutic applications. ETAMERS create precise repairs without causing undesired insertions and deletions. ETAMERS are also employed as an improved donor DNA for use with programmable nucleases such as CRISPR-Cas9.


ETAGEN Pharma was founded in 2014 by Tod Woolf, Ph.D. and Richard Hogrefe, PhD. ETAGEN’s technology treats disease by selectively editing out mutated sequences or editing in protective genomic variants. ETAGEN offers field-specific licenses to its foundational editing platform IP for BASE Editing, PRIME editing, oligo-only editing and for use as enhanced donor DNA in combination with programmable nuclease-mediated editing.


Glenn Wachler

President and CEO

Glenn Wachler is a serial entrepreneur having served in sales, business development and finance roles.  He is the creator of LIfeLinks™ modular jewelry and  co-inventor of Choice-Packs™.   He has founded and operated a successful estate jewelry brokerage, real estate finance company and food service company. He has a BA degree in General Business Administration from Michigan State University.


Tod Woolf, Ph.D.

Co-Founder, Business Advisor

Dr. Woolf co-authored the first article using the term Therapeutic Editing™ and demonstrating efficient Therapeutic Editing in a model cellular system in 1995. Dr. Woolf has developed and commercialized innovative biomedical platforms and products employed throughout the biopharmaceutical industry including BASE editing (Toward the therapeutic editing of mutated RNA sequences. | PNAS), MOD mRNA Therapeutics™ and vaccines(WO1999014346A2 – SENSE mRNA THERAPY – Google Patents), Stealth™ RNAi (Stealth RNAi siRNAs | Thermo Fisher Scientific – US), Self-Delivering RNAi™  (Self-deliverable siRNA, GalNAc siRNA ( and Next Generation Antisense™. Dr. Woolf completed his Ph.D. thesis in Professor Doug Melton’s laboratory at Harvard University. He co-founded and served as CEO at Sequitur (acquired by Life Technologies) and co-founded RXi Pharmaceuticals with Prof. Craig Mello. His teams have raised over $50M in equity financing and generated over $150M in non-dilutive revenues through alliances, licenses, grants and research product sales.  From 2016-2019 he served as a Technology Licensing Officer at MIT. Since 2019 he has served as the Executive Director of Technology Ventures at Beth Israel Deaconess Medical Center in Boston, Mass and he is a Lecturer on Medicine at Harvard Medical School.


Richard Hogrefe, Ph.D.

Co-Founder and Technology Advisor

Dr. Hogrefe, co-founded and was CEO of TriLink Biotechnologies for 20 years, a leading manufacturer of nucleic acid reagents and therapeutics company that was sold to Maravai Life Sciences in 2016. Dr. Hogrefe performed his graduate work with Prof. Robert Letsinger, the originator of solid support DNA synthesis chemistry. His academic and industrial career has focused on the synthesis of challenging RNA and DNA drugs and probes. He is author of over 40 patents and research articles, and has served on the editorial board of the journal Oligonucleotides. Dr. Hogrefe’s team at TriLink has provided synthesis support to virtually every major player in oligonucleotide therapeutics.




Prof. Richard Boyce, M.D., Ph.D.

Prof. Boyce has an appointment at Harvard University with a laboratory at Massachusetts General Hospital. He received his BS from MIT and his MD/Ph.D. from the University of Michigan. He is an expert on gene therapy and genetic diseases and he has served as an advisor to numerous biotechnology companies.  Dr. Boyce cloned the dystrophin brain promoter and performed early work with truncated forms of active dystrophin for gene therapy.  Prof. Boyce created a baculovirus expression system for mammalian cells that has been broadly commercialized.

James McSwiggen, Ph.D.

Dr. McSwiggen is an expert in translational nucleic acid therapeutics and bioinformatics and serves as the CEO of the RNA Society.  He is a co-inventor on hundreds of patents and patent applications and was the lead inventor on the “McSwiggen” patent that forms the basis of Alnylam’s 3rd Generation Chemistry.  He formerly served as a Research Scientist at RaNA, Quark and SIRNA Merck.  Dr. McSwiggen completed his post-doctoral fellowship in the laboratory of Nobel Prize winner Prof. Thomas Cech.

Prof. Eric Kmiec, Ph.D.

Dr. Kmiec founded and directs the Gene Editing Institute at the Helen F Graham Cancer Center and Research Institute in Newark, Delaware and is a Professor at the University of Delaware. He has also served as Director of the Laboratory of Applied Genomics at the Delaware Biotechnology Institute. His lab was the first to achieve genome editing in mammalian cells with oligonucleotides and he has co-authored over 30 patents and 140 research articles in the genome editing field.



ETAGEN’s Therapeutic Editing™ drugs, called ETAMERS™, specifically bind to and permanently correct disease-causing nucleic acid sequence variants in tissues. ETAGEN’s platform employs chemically modified synthetic ETAMERS that act as both the guide and template for genome and mRNA editing.  ETAMERS can be used with or without programmable sequence-binding moieties such as CRISPR-Cas9.  ETAGEN’s approach has the following beneficial properties for therapeutic development:

  • Readily manufactured by chemical synthesis
  • More readily delivered to target tissues in vivo than protein-containing editors
  • Non-immunogenic allowing for multiple dosing
  • Do not require dsDNA breaks that can lead to undesired insertions and deletions
  • Strong IP with freedom to operate


ETAGEN offers field-specific licenses to its foundational editing platform IP for BASE Editing, PRIME editing, oligo-only editing and for use as enhanced donor DNA in combination with programmable nuclease-mediated editing.  ETAGEN’s allowed and pending patents have early (2014-2017) priority dates:

  • ETAGEN-001:  Compositions and methods for editing nucleic acids in cells utilizing oligonucleotides. Inventors: Tod M. Woolf, Alexandre Lebedev and Richard I. Hogrefe:  PCT/US2015/065348 EU, JP, China and US 16/687,665
  • ETAGEN-002:  Improved methods for genome editing with and without programmable nucleases. Inventor: Tod M. Woolf:  PCT/US2017/031381 EU, JP, China and US

Available licensing fields for research and therapeutic applications:

1. Repeat single ETAMER treatments without programmable nucleases (no target DNA Cleavage).

2. ETAMER with “Chemical CRISPR”™ without programmable nuclease (no target DNA cleavage, higher efficiency per treatment compared to MODE 1.

3. ETAMER 3rd Gen Donor DNA with programmable nuclease to increase editing frequency compared to unmodified donor DNA.

4. DNA Containing ETAMER crRNA plus Cas9 that acts as a guide and donor to dramatically enhance precise editing efficiency (i.e. donor-guide and Prime editing).

5. Editing DNA or RNA by nucleobase modification (now called BASE editing).


E-Mail ETAGEN to obtain an updated presentation pdf.



Selected Publications and Patents Relevant to Therapeutic Editing™ by ETAGEN’s Team Members:

Woolf, TM, Rivera-Torres, N, Hogrefe, R and Kmiec, E. Genome editing with third-generation chemically modified oligonucleotides. Poster at the National Cancer Institute RNA Biology Symposium, 2021.

Woolf, TM, Gurumurthy, CB, Boyce F, Kmiec EB. To Cleave or not to Cleave:  Therapeutic Editing with and without Programmable Nucleases. Nature Reviews Drug Discovery 2017 Mar 17;16:296. PMID: 28303022

Rivera-Torres N, Strouse B, Bialk P, Niamat RA, Kmiec EB. The Position of DNA Cleavage by TALENs and Cell Synchronization Influences the Frequency of Gene Editing Directed by Single-Stranded Oligonucleotides. PLoS One 2014;9: e96483. (demonstrates gene editing with ETAMERS™ is enhanced by site-directed chromosomal cleavage)

Eric B. Kmiec. Is the age of genetic surgery finally upon us? Surgical Oncology 24 (2015) 95e99. (review on genome editing)

Woolf TM, Chase JM, Stinchcomb D. Toward the therapeutic editing of mutated RNA sequences. Proceedings of the National Academy of Science 92(18):8298-302, 1995. (first paper using the term nucleic acid “editing” in reference to therapeutics and demonstrating  editing of mutated mRNA)

Woolf, TM. Therapeutic Repair of Mutated Nucleic Acid Sequences. Nature Biotechnology, Vol 16:341-344, 1998. (review of earliest therapeutic editing work and generalizing the concept of genome editing by strand-invasion).

Woolf, Tod, Melton, Doug, and Jennings, Charles. Specificity of antisense oligonucleotides in vivo. Proceedings of the National Academy of Science 89:7305-7309, 1992. (first publication demonstrating mechanism of off-target effects with oligonucleotides related to seed sequences)

Woolf, TM. It’s Not the Size, It’s the Potency. Nature Biotechnology, August 1996, 14, 824, 1998. (invited commentary on the seminal paper of Richard Wagner et al. demonstrating efficient delivery of “naked” chemically modified antisense oligonucleotides to cells in vitro).

Woolf, TM, Wiederholt, KA and Taylor, MF. Sense mRNA Therapeutics. Published Patent Application US 20090093433, filed 1998. (first description of chemically modified mRNA for therapeutics, now commonly employed for delivering editing proteins)

Li Liu, Michael C. Rice and Eric B. Kmiec. In vivo gene repair of point and frameshift mutations directed by chimeric RNA/DNA oligonucleotides and modified single-stranded oligonucleotides. Nucleic Acids Research, Vol. 29:4238-4250, 2001. (first demonstration of the use of 2nd generation chemically modified single-stranded oligonucleotides (ETAMERS) for genome editing in eukaryotic cells)

Ferrara L, Kmiec EB. Camptothecin enhances the frequency of oligonucleotide- directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination. Nucleic Acids Res 2004;32:5239e48. (early demonstration that genomic DNA strand breakage enhances efficiency of editing by ETAMERS)

Erin E. Brachman, Eric B. Kmiec. Gene repair in mammalian cells is stimulated by the elongation of S phase and transient stalling of replication forks. DNA Repair 4:445–457, 2005. (demonstration that ETAMER editing efficiency can be enhanced by modification of the cells state)

Eric B Kmiec, Howard B Gamper, Michael C Rice. U.S. Pat. No. 7,258,854 B2, Targeted Chromosomal Genomic Alterations with Modified Single Stranded Oligonucleotides (2007) (discloses 2nd generation chemically modified single-stranded therapeutic editing oligonucleotides (ETAMERS), exclusively licensed to ETAGEN)

Kmiec, EB, Gamper, HB, and Rice, MC. US Pat. No. 7,226,785 Targeted Chromosomal Genomic Alterations with Modified Single Stranded Oligonucleotides (2007) (discloses 2nd generation chemically modified single-stranded therapeutic editing oligonucleotides (ETAMERS), exclusively licensed to ETAGEN)

Julia U. Engstrom and Eric B. Kmiec. DNA replication, cell cycle progression and the targeted gene repair reaction. Cell Cycle 7:10, 1402-1414; 15 May 2008. (demonstrates dramatic increase of editing efficiency by ETAMERS in synchronized cells)

Woolf, TM , Samarky, D. and Cardia, J. Self-Delivering RNAi Compounds. Drug Delivery Technology.  Vol. 10 No. 7 Sept. 2010. (describes chemistries for achieving self-delivery of oligonucleotides in cells)



Taming the Helix: The First 40 Years of RNA Therapeutics. Tod Woolf presenting the opening keynote address at the Oxford Global Conference on RNA Therapeutics & Delivery US in Boston Mass., June 2023.

Origins of the MOD mRNA Platform For Therapeutics And Vaccines. Tod Woolf presenting at the RNA THERAPEUTICS & DELIVERY, US in Boston Mass., June 2022.

Editing with & without Programmable Nucleases, Tod Woolf presented at NextGen Omics in Boston Mass., March 2022.

Taming The Helix: The First 40 Years Of RNA Therapeutics. Tod Woolf Presenting Session Keynote Address RNA Therapeutics & Delivery US in Boston Mass., June 2021.

Taming the Helix: The First 40 Years of RNA Therapeutics, Online, Harvard Initiative for RNA Medicine at BIDMC, Tod Woolf, Seminar Speaker, Dec 8th, 2020.

Chemically Modified Polynucleotides For Inhibiting, Expressing and Repairing Nucleic Acids: Then And Now. Tod Woolf Session Keynote Presenter, 4th Annual Genome Editing USA Congress online, April 2020.

Sarah Reardon. Step aside CRISPR, RNA editing is taking off, News Feature, 578: 24-27. Nature. 2200 578:24-27. (A Nature news feature noted the first work on mRNA BASE editing was performed by Tod Woolf’s team at Ribozyme Pharmaceuticals.)

Eisenstein, M., Garber, K., Seydel, C. et al. Nature Biotechnology’s academic spinouts of 2019. Nat Biotechnology 38, 546–554 (2020). Noted, “back in 1995, Tod Woolf, Jennifer Chase and Dan Stinchcomb first demonstrated how to edit RNA with oligonucleotides”

To Cleave Or Not To Cleave: Therapeutic Editing Without Programmable Nucleases. ETAGEN CEO Tod Woolf, Seminar Speaker at the 2nd Annual Genome Editing USA Congress in Boston Mass., May 10-11th 2018.

The Rollercoaster Ride of RNA Biotech Companies: From Obscurity to a $20B Industry. ETAGEN CEO, Tod Woolf Seminar at MIT, January 17th, 2018.

Optimizing Oligonucleotide Mediated Editing. ETAGEN CEO Tod Woolf, Seminar Speaker at the CF Foundation Conference on New Technologies Advancing Toward a One-Time Cure Savannah, GA, May 2016.

Introduction to Genome Editing and Engineering. ETAGEN CEO Tod Woolf at the Genome Editing & Engineering Conference in San Diego, CA, February 18th, 2016.

Cleaving, Expressing and Repairing Nucleic Acids for Therapeutic Applications at the 13th International RNAi/MicroRNAs/Stem Cells & Genome Editing Meeting. ETAGEN CEO Tod Woolf, May 4-5th, 2016 Boston, Mass.

Going in alone: Etagen is editing genes using oligos alone Biocentury, Katen Tkach, Staff Writer, March 31st, 2016. (BioCentury – Going in alone)

Oligonucleotide-Directed Therapeutic Editing. ETAGEN CEO Tod Woolf at EuroTIDES, Berlin, Germany, November 18, 2015.

Genome Editing with Chemically Modified Oligonucleotides. ETAGEN CEO Tod Woolf Biotechnology Industry Organization International Convention partnering forum in Philadelphia, Penn., Tuesday, June 16th, 2015.

ETAGEN Pharma to Launch Single-Agent Therapeutic Editing Platform with Presentation at the 2015 BIO International Convention (

Genome Editing Nuclease Specificity: Defining Off-Target Effects/Using Genome Editing for Therapeutic Applications. ETAGEN CEO Tod Woolf served as a member of the panel discussion at the IBC Conference on Genome Editing Applications in Boston, March 19th, 2015. Taming the Helix: The First 40 Years of RNA Therapeutics.

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