Patent Snapshot: Averna’s tech on safer, more precise gene insertion

Averna Therapeutics is a Boston‑based biotechnology company developing genomic medicines that insert therapeutic genetic material into defined locations within the human genome.

Targeted insertion at safe harbor sites provides an advantage over conventional gene editing methods such as CRISPR, which rely on nucleases that create double-strand DNA breaks and can produce off-target effects. Averna’s platform enables programmable, potentially redosable, and titratable gene insertion across multiple disease areas, including rare genetic disorders, cancer, and autoimmune conditions.

Unlike many biotech firms with traditional named drug candidates, Averna focuses on its platform technology rather than specific marketed assets. Its RNA and lipid nanoparticle (LNP) platform is designed to deliver therapeutic genes to “safe harbor” sites in the genome, regions capable of accepting new genetic instructions without disrupting other cellular functions. 

Averna’s Series A funding

Averna was previously known as Exsilio Therapeutics and adopted the new name in early 2025. It emerged in June 2024 with an $82 million Series A financing led by Novartis Venture Fund and Delos Capital, with participation from investors including OrbiMed, Insight Partners, J.P. Morgan Life Sciences Private Capital, and CRISPR Therapeutics, to advance its gene insertion platform.

Averna’s core invention

Gene therapy delivers therapeutic genes or corrected cells to treat genetic diseases, but existing methods such as CRISPR and viral vectors can be imprecise, inefficient, or carry permanent elements, highlighting the need for more accurate and reliable approaches. 

Averna addresses this in WO2024116156 by using RNA-templated DNA synthesis and chromosomal insertion via engineered retrotransposon enzymes. This system produces therapeutic DNA inside the cell without double-strand breaks or viral integrases, creating a non-viral, enzyme-mediated genome-writing approach.

The platform uses a two-component, RNA-only system. One RNA encodes the therapeutic transgene flanked by non-LTR retrotransposon-derived regions, while a second encodes an engineered retrotransposon-derived driver protein. Inside the cell, the driver RNA is translated into a multifunctional enzyme, and the gene delivery RNA serves as a reverse transcription template. This converts therapeutic RNA directly into integrated DNA, eliminating the need for plasmids, episomal persistence, or viral genomes. The RNA-only design supports lipid nanoparticle delivery and repeat dosing, as no long-lived vector remains after insertion.

At its core are engineered retrotransposon proteins that act as programmable gene insertion enzymes. These modular proteins combine reverse transcriptase, endonuclease activity, nuclear targeting signals, and optional domains to enhance integration. Variants incorporating amino acid changes or fused domains enhance DNA processing, repair, and binding. The patent also covers the corresponding nucleic acids and methods for editing genes, creating a reusable genome-writing platform for gene therapy.

Averna Therapeutics: Patenting Activity

Averna’s  patent activity shows a clear timeline of how its technology has matured. The 2022 priority filing represents the company’s early effort to secure protection around its core genome insertion platform. This was an important foundational step that established ownership over the basic mechanism behind its approach to inserting therapeutic DNA in a controlled manner.

The following year, Averna appears to be enhancing both the performance and robustness of its platform, a common progression once a core concept has been validated. The 2024 filing, in particular, signals a shift toward practical use. Rather than focusing solely on platform protection, Averna positions its technology within specific therapeutic contexts, particularly immune cell engineering. This reflects a progression from enabling technology to concrete applications that could support future product pipelines and strategic partnerships.

A new generation of engineered drivers for genome integration

As mentioned previously, many current genome integration methods, especially those using retroelements, lack precision. Newly introduced genes may integrate at unintended genomic locations or fail to function as intended. This can reduce therapeutic effectiveness and increase safety risks, underscoring the need for more accurate and reliable approaches to inserting therapeutic genes into the genome.

Averna addresses this challenge by developing improved “driver” proteins that function as advanced delivery engines for gene insertion. These engineered proteins are designed to enhance DNA binding, localize more efficiently to target cellular compartments, and interact more effectively with endogenous DNA repair pathways. As a result, gene insertion becomes faster, more accurate, and more reliable than with existing approaches.

Using these drivers, the system also incorporates the therapeutic gene along with specialized sequence elements that guide where insertion occurs. The complete system can be delivered using lipid nanoparticles, which facilitate cellular uptake of the genetic material. Together, this approach provides a safer and more controlled method for introducing functional genes, improving the practicality and effectiveness of gene therapy.

WO2025074310, titled “Engineered retrotransposable element proteins for gene delivery and insertion”, was filed on October 3, 2024, and was published on April 10, 2025. The application lists Devin Trudeau, Yaron Ben Shoshan Goleczki, Aaron Gordon, Noga Kowalsman, and Orshay Gabay as inventors. 

Targeted in vivo delivery for practical T cell therapies

Engineered T cell therapies enable the immune system to combat cancer and other diseases. Currently, most such treatments rely on ex vivo workflows in which cells are removed from the patient, genetically modified in a laboratory setting, and then reinfused. This process is time-consuming, costly, and operationally complex. In vivo modification presents its own risks, particularly if unintended cell populations are affected. Consequently, there is a strong need for faster, safer, and lower-cost methods to reprogram T cells directly in patients.

The solution introduces a method for placing genetic instructions directly into immune cells in vivo. It uses engineered genetic material encoding immune receptors such as CARs, TCRs, or TRAMs, which enable T cells to recognize and eliminate diseased cells. The system functions as a guided genome-writing tool that installs these instructions into T cell DNA, supporting durable therapeutic effects without the use of traditional viral vectors.

For clinical applicability, the genetic material is delivered via lipid nanoparticles, which are nanoscale lipid-based carriers that facilitate cellular entry. These nanoparticles may be functionalized with antibodies to preferentially target T cells, and the cells themselves may be conditioned to enhance uptake and integration. Together, these strategies enable direct in vivo reprogramming of T cells in a more targeted, durable, and scalable manner, reducing complexity and cost while improving safety.

WO2025229499, titled “Compositions and methods for modulating t cells”, was filed on April 28, 2025, and was published on November 6, 2025. The application lists David Bassan, Ruben Alvarez Rodriguez, Devin Trudeau, Maya Ron, and Yaron Ben Shoshan-Goleczki