mRNA moment for single stranded DNA.
Co-develop long modified ssDNA with our scientists. Together, we define the application, assess chemistry feasibility and agree the analytical and biological work. Modification technology is available to selected partners. Participation and scope are agreed for each partnership.
We have not yet demonstrated that Moligo’s modified long donors outperform matched unmodified donors.
Explore the partnership programmeOur ssDNA synthesis service continues. Order custom linear or circular DNA, or start with an existing construct.
Discuss your sequence, length, format and release specification with the team.
Quality control & release criteriaChemistry adds another dimension to donor design. Internal modification lets us investigate properties across the molecule, beyond protection at its ends.
Our process uses a modified nucleotide pool. Incorporation is distributed statistically throughout the strand, with dose control by base identity.
How internal modification worksEnd adaptors protect the ends. A modified oligonucleotide adds a local patch. Moligo incorporates modified nucleotides during synthesis, distributing chemistry throughout long ssDNA.
This expands what can be investigated at kilobase length: composition across the molecule, alongside linear or circular format. The programme brings synthesis, characterisation and application testing into one collaboration.
Incorporation is statistical. We control the reaction pool, not individual positions. The performance of modified long donors against matched unmodified controls remains to be demonstrated.
Why chemistry
Every approved single-strand oligonucleotide drug since 2013 carries five to seven distinct chemistries in one molecule, because the requirements pull against each other and no single modification satisfies more than one or two of them.
Every one of those molecules is also under 40 nucleotides. A gene-length donor has never had access to that design language.
| Drug | Year | Length | Distinct chemistries |
|---|---|---|---|
| Fomivirsen | 1998 | 21 nt | 1, phosphorothioate only. Commercially withdrawn |
| Mipomersen | 2013 | 20 nt | 5 |
| Nusinersen | 2016 | 18 nt | 4 |
| Inclisiran | 2021 | 21/23 nt | 6 |
| Tofersen | 2023 | 20 nt | 6 |
| Eplontersen | 2023 | 20 nt | 7 |
| Donidalorsen | 2025 | 20 nt | 7 |
Inotersen and eplontersen have identical sequences. The difference between them is added chemistry: selective phosphorothioate-to-phosphodiester swaps and a GalNAc conjugate. That change converted a weekly subcutaneous injection carrying a boxed thrombocytopenia warning into a monthly injection with better tolerability.
Sequence held constant. Chemistry changed. A different medicine. This is the design language that stops at about 200 bases, and the reason we work on composition at kilobase length.
In a published short-donor study, internal phosphorothioate modification gave 41 ± 15% HDR, versus 24 ± 6% for end-modified and 15 ± 5% for unmodified donors.
The experiment used airway cells, the CFTR locus and the DNA-PK inhibitor AZD-7648.
Kanke et al., Nucleic Acids Research, 2024. These were short donors with defined spacing, not Moligo’s statistically modified long ssDNA.
The people behind Moligo
CEO & founder
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Continuity
IDT discontinued Megamer single-stranded DNA fragments on 31 December 2025. If that was your HDR donor, the alternatives differ in length ceiling, format and release specification, and none of them is a drop-in equivalent on all three.
Send us the construct and we will work through the differences with you before you commit.
Talk to our scientistsTell us about your sequence, application and the chemistry you want to investigate.
