Next-Generation Gene Writing is Bridging the Gap Between Tools and Cures

Endpoints News -December 29, 2025-The rapid rise and fall of Tome Biosciences has become a cautionary tale for the biotechnology industry, highlighting a growing tension between the pursuit of the “ultimate” gene-editing tool and the practicalities of developing medicine. Launched with $213 million in late 2023, the startup promised a “final chapter” in genomic medicine before shuttering just eight months later, leaving the field to grapple with the limitations of hyper-complex genetic systems.

The Complexity Trap

Tome’s core technology, known as PASTE, attempted to solve the industry’s greatest challenge: the precise insertion of large DNA sequences. While first-generation CRISPR tools act as molecular scissors to “knock out” genes, and base editors act as “pencils” to fix typos, Tome’s tool functioned like a “GPS-guided heavy lifter.” It combined:

• AAV (Adeno-Associated Virus): To deliver the replacement gene.

• Prime Editing: To write a 40-letter “landing pad” into the genome.

• Integrases: Viral enzymes designed to drop the new gene into that specific pad.

Despite achieving success in monkey studies—potentially offering a cure for Phenylketonuria (PKU)—the system required two different lipid nanoparticles, an AAV vector, and multiple RNA guide molecules. This unprecedented complexity scared off investors in a tightening capital market, where stocks of established peers like Intellia and Metagenomi dropped by over 60% in 2024.

A New Wave of “Simpler” Competition

The collapse of Tome has not stopped the race for a “one-size-fits-all” gene replacement tool. A new generation of startups is now leveraging Artificial Intelligence to design proteins that are inherently simpler than the Tome “contraption.”

• Stylus Medicine: Recently disclosed $85 million in funding to develop programmable integrases that work without the need for CRISPR or landing pads.

• Averna Therapeutics: Raised $82 million in June 2024 to harness “jumping genes” (retrotransposons), aiming for a therapy delivered entirely via RNA-filled nanoparticles, potentially eliminating the need for AAV.

• Basecamp Research: Has recruited former Tome Chief Scientist John Finn to use AI to design bespoke integrases that target human DNA directly.

The Human Impact vs. Technical Ambition

While the industry chases the “holy grail” of large-scale gene insertion, some scientists are finding success by scaling down. In Philadelphia, researchers recently used base editing to save the life of a single infant (Baby KJ) by fixing a unique mutation. This success has sparked a debate: should resources go toward bespoke, individual cures or the decade-long pursuit of a universal “final tool”?

“Everyone has been too ambitious,” noted Kiran Musunuru, one of the scientists behind Baby KJ’s treatment. As more than 20 companies now crowd the gene-insertion space, the field faces a reckoning: the “final chapter” of genomic medicine cannot be written until the technology is simple enough to be manufactured at scale and safe enough for the thousands of rare diseases that currently have no options.