Full Circles Therapeutics Highlights Circular Single-Stranded DNA Platform Enabling Immune-Evasive Genome Writing in Nature Study

CAMBRIDGE, Mass., March 11, 2026 /PRNewswire/ -- Full Circles Therapeutics today announced that its circular single-stranded DNA (cssDNA, C4DNA™) technology platform has been highlighted as a key enabling component of a new genome engineering strategy reported in Nature. The study, conducted in collaboration with Benjamin Kleinstiver, PhD, and Connor Tou, PhD, at the Center for Genomic Medicine at Massachusetts General Hospital, demonstrates a method for inserting gene-scale DNA into the genome while avoiding the strong innate immune responses typically triggered by conventional double-stranded DNA donors.

The work represents an important step toward safe, virus-free genome writing therapies capable of delivering entire therapeutic genes rather than correcting individual mutations. Full Circles' proprietary C4DNA™ technology enables the scalable production of large, highly pure circular single-stranded DNA molecules that serve as immune-evasive genetic payloads for genome engineering.

Unlike conventional double-stranded DNA templates, these molecules can carry full-length therapeutic genes together with regulatory elements, including promoters capable of driving durable expression in target cells.

"Circular single-stranded DNA provides a fundamentally different genetic payload compared with conventional double-stranded DNA or transient mRNA approaches," said Howard Wu, PhD, Co-founder, CEO and Chief Scientific Officer of Full Circles Therapeutics. "By enabling kilobase-scale gene writing with immune-evasive DNA donors, this work highlights the potential of cssDNA as a paradigm-shifting modality for next-generation non-viral genomic medicine."

The genome integration system described in the study, termed INSTALL, combines recombinase enzymes with specially engineered cssDNA donors. In this design, the C4DNA molecule contains a largely single-stranded circular backbone that helps evade cytosolic double-stranded DNA sensing pathways responsible for triggering inflammatory responses. A short engineered double-stranded segment is incorporated to provide a recognition site for recombinase enzymes, which naturally act on double-stranded DNA substrates. Once inside the nucleus, the recombinase recognizes this duplex region and catalyzes precise insertion of the larger genetic payload into a defined genomic locus assisted by second-strand synthesis. By minimizing the amount of double-stranded DNA while preserving recombinase compatibility, the system enables efficient gene-scale DNA integration while avoiding the toxicity typically observed with conventional donors.

Traditional genome editing approaches often attempt to correct individual mutations, requiring highly customized engineering strategies such as base editing or prime editing systems to target specific variants. However, many genetic diseases, including cystic fibrosis and ß-thalassemia, are caused by hundreds of distinct mutations within the same gene across patient populations. A gene replacement strategy enabled by C4DNA could instead insert a healthy copy of an entire gene, such as CFTR or HBB, into a defined genomic location, providing a mutation-agnostic therapeutic approach that addresses the root genetic cause of disease.

Unlike mRNA therapeutics, which produce transient protein expression and typically require repeat dosing, cssDNA enables gene-scale payloads capable of supporting durable, promoter-controlled expression following genomic integration. The circular single-stranded architecture also helps evade cellular double-stranded DNA surveillance pathways, reducing innate immune activation.

"This immune-evasive property allows C4DNA to effectively get under the radar of cellular dsDNA surveillance systems," Wu explained. "That opens the door to safer delivery and potentially improved pharmacokinetics compared with conventional mRNA-based approaches."

Importantly, the Nature study demonstrates that C4DNA-based donors can enable kilobase-scale gene insertion in vivo when combined with recombinase systems and lipid nanoparticle delivery, providing a potential path toward virus-free gene integration therapies.

A key advantage of the technology is compatibility with non-dividing or slowly dividing cells, including muscle and neurons. Earlier genome insertion approaches largely depended on homology-directed repair active during cell division. In contrast, C4DNA-enabled genome writing may allow integration in post-mitotic tissues, expanding opportunities to treat neurological and neuromuscular diseases.

Beyond genetic diseases, Full Circles Therapeutics is advancing C4DNA-enabled applications in oncology and immunotherapy. The company is developing in vivo cell engineering approaches, where lipid nanoparticles deliver C4DNA payloads that program immune cells directly inside the body, potentially simplifying manufacturing and expanding patient access to cell therapy living drugs.

With a growing intellectual property portfolio covering the therapeutic use of circular single-stranded DNA, Full Circles Therapeutics is working with partners to advance investigator-initiated clinical programs targeting both solid tumors and hematologic malignancies.

"Genome writing represents the next frontier of precision medicine, and C4DNA may be the name of the game," said Richard Shan, PhD., Co-founder and Chairman of Full Circles Therapeutics, "Our mission at Full Circles is to build the DNA platform that makes these therapies practical, scalable, affordable, and broadly accessible worldwide."

Contact for Licensing Partnership Inquiries

For Media & Licensing Inquiries:
Flora Zhang
Director of Communications, Full Circles Therapeutics Inc.
Phone: (410) 733-0130
Email: [email protected]

About Full Circles Therapeutics

Full Circles Therapeutics is a pioneering biotechnology company advancing genome engineering through innovative, non-viral gene editing technologies. Its proprietary cssDNA platform is designed to enable safer, more efficient, and scalable genetic modifications, revolutionizing next-generation cell and gene therapies.

For more information, visit www.fullcirclestx.com.

SOURCE Full Circles Therapeutics