The Problem With Permanent
Most gene therapy companies edit DNA. Jacob Borrajo thinks that's a mistake. Not a small mistake - a foundational one, the kind that limits an entire field for decades. DNA edits are permanent. They're heritable. Off-target mutations don't wash out. And when you're trying to treat a disease where thousands of patients each carry a slightly different genetic variant, a DNA-based single product quickly becomes a logic problem with no good answer.
Borrajo spent years inside some of the densest concentrations of CRISPR expertise on Earth - first at MIT, then at the Broad Institute - watching the field converge on DNA editing as if it were destiny. He took a different bet. RNA degrades. That's not a flaw. That's the design. Build your therapy around RNA, and you get edits that are reversible, durable enough to matter clinically, and broad enough to treat the messy genetic diversity that real patient populations actually have.
"We're creating an entirely new ability to durably rewrite RNA, and thereby restore human health in many disease settings. Our technical approach leverages novel, iteratively engineered Cas-based systems for durable RNA editing, creating significant advantages over editing DNA, which can lead to permanent, off-target mutations."- Jacob Borrajo, on Amber Bio's founding vision
Splice Editing: How It Works
The platform Amber Bio built is called splice editing. It combines CRISPR-mediated RNA targeting with the cell's own splicing machinery - the endogenous mechanisms that already exist inside every human cell to process RNA transcripts. The result: programmable, large-scale RNA edits that can span kilobases - thousands of base pairs - in a single, reversible step. It's not a small tweak to existing CRISPR approaches. It's a different architecture.
DNA Editing (Conventional)
- Permanent edits - cannot be undone
- Risk of heritable off-target mutations
- One mutation = one therapeutic
- Limited edit size (typically small)
- High regulatory scrutiny on irreversibility
RNA Writing (Amber Bio)
- Reversible - RNA naturally degrades
- No permanent off-target DNA changes
- One product treats diverse mutations
- Multi-kilobase edits in a single step
- Scalable across high allelic diversity
The key word in that description is "scalable." Genetic diseases rarely come in clean editions. A disease like certain inherited retinal dystrophies can be caused by hundreds of different mutations across multiple genes. Under conventional gene therapy logic, that means hundreds of different therapeutic products, each developed, tested, and approved independently. The economics alone make most of those diseases commercially untouchable. Amber Bio's platform collapses that problem: because RNA editing works across allelic diversity, a single therapeutic can reach patients regardless of which specific mutation they carry.
Amber Bio Platform Highlights
- Multi-kilobase editing: Can rewrite thousands of bases in a single programmable step - scales beyond what conventional CRISPR approaches can do.
- Endogenous splicing machinery: Leverages cellular RNA processing pathways already operating inside the patient's cells, reducing foreign component burden.
- Allelic diversity coverage: One therapeutic product can treat patients with many different underlying mutations - solving gene therapy's scalability math.
- Machine learning integration: AI foundation models optimize RNA targeting, compressing the design-test-iterate cycle.
- Reversibility: RNA targets naturally degrade, giving the platform a built-in safety buffer that DNA editing lacks.
- Primary targets: Inherited retinal diseases, CNS disorders, and monogenic diseases with high allelic diversity.
Three Companies Before Forty
Jacob Borrajo's path to Amber Bio isn't linear - it's serial. He started building companies while still completing his PhD, which at MIT is either a sign of ambition or poor time management. The evidence suggests the former.
His first company, Scribio, launched around 2015 while he was a doctoral student. It focused on novel CRISPR/Cas delivery technology for synthetic biology - early signal that Borrajo wasn't simply interested in applying existing tools. He wanted to build the delivery infrastructure that made those tools usable. He ran Scribio as CEO and wrapped it around 2018, the same year he co-founded Coral Genomics.
Coral emerged from the Broad Institute, where Borrajo crossed paths with Atray Dixit - a collaboration that turned into a company focused on RNA sequencing tools for live cells. As CTO at Coral, Borrajo was solving a different but related problem: measuring what RNA is doing inside living biology in real time. That measurement experience would matter later. You can't write RNA therapeutics at scale without knowing how to read what RNA is doing.
The Round That Got Oversubscribed
Amber Bio's $26 million seed round closed in August 2023. It was oversubscribed - a fact worth noting in a period when biotech funding was contracting and investors were repricing risk. The co-leads were Andreessen Horowitz Bio + Health and Playground Global, two firms that don't anchor rounds without strong conviction.
What made the round unusual was the strategic participation. Eli Lilly - one of the largest pharmaceutical companies in the world - invested. So did the Retinal Degeneration Fund, a specialist nonprofit investor focused specifically on inherited retinal diseases. When the RD Fund writes a check, the ophthalmology field pays attention. Their investment in Amber Bio functioned as a signal from the patient community itself: this approach is worth betting on.
The round's construction - top-tier generalist VCs plus pharma plus patient-focused strategics - tells a specific story. This isn't a company selling a technology platform. It's a company building toward therapeutic products, with investors who can help it get from molecular biology to clinical reality.
The Family Tree
Amber Bio's co-founder Basem Al-Shayeb completed his PhD at UC Berkeley and is an academic descendant of Jennifer Doudna - the biochemist who won the Nobel Prize in 2020 for her work developing CRISPR-Cas9. In the compact world of gene editing, these lineages matter. They represent not just training but networks, assumptions about what problems are worth solving, and instincts about how to approach molecular biology.
Borrajo's own lineage runs through MIT's Blainey Lab and the Broad Institute - the institutional home of much of the CRISPR research that followed Doudna's foundational work. The fact that Amber Bio brought together researchers from both sides of the Berkeley-MIT axis in gene editing isn't coincidence. It's a deliberate integration of complementary scientific frameworks.
The Research Behind the Company
In August 2023, Borrajo's team published their foundational paper on bioRxiv: "Programmable multi-kilobase RNA editing using CRISPR-mediated trans-splicing." The preprint laid out the mechanism and evidence base for splice editing. In biotech, companies often form first and publish later - the publication timing here, coinciding with the funding announcement, signaled that the science had cleared internal review and was ready for peer scrutiny.
Targeting the Undruggable
The term "undruggable" gets used a lot in pharma circles, often as a polite way of saying "we gave up." It refers to diseases or molecular targets where conventional therapeutic approaches - small molecules, monoclonal antibodies, even first-generation gene therapies - can't get traction. The reasons vary: wrong target size, too much patient heterogeneity, too many mutations to address cost-effectively, too much off-target risk for a permanent edit.
Amber Bio's splice editing platform is specifically designed to work in the spaces where those objections dissolve. Heterogeneity? The platform handles diverse mutations. Permanence? RNA degrades. Off-target risk? No DNA cleavage. Large edit requirements? Multi-kilobase is the point. Each technical property of the platform corresponds to a specific barrier that was keeping certain diseases out of the gene therapy market.
- Targets inherited retinal diseases - conditions where hundreds of different mutations affect thousands of patients
- Central nervous system diseases - where the irreversibility of DNA editing creates serious safety questions
- Monogenic diseases with high allelic diversity - where one-mutation-one-drug economics never worked
- Patient populations currently served by zero approved gene therapies
Artisanal Science at Scale
One of the stranger tensions in biotech is between the precision required at the molecular level and the scale required to make a business. A therapy that works beautifully in 12 patients doesn't automatically work in 12,000. Most of the difficulty in gene therapy development lives in that gap - in manufacturing, delivery, regulatory strategy, and the sheer logistics of treating real patients in real hospital systems.
Borrajo talks about "artisanal science" as a starting point - the careful, specific, labor-intensive work of understanding molecular mechanisms before assuming they'll scale. It's a disposition that comes from spending years in academic labs where rigor is the culture, not just a constraint. But Amber Bio's commercial thesis depends on eventually escaping the artisanal model. The splice editing platform's value is precisely that it can become a platform - a repeatable approach across disease areas rather than a series of bespoke, one-off programs.
With 22 people and a $26 million seed, the company is still in the period where those two modes coexist. The science is necessarily careful and specific. The platform architecture is designed for breadth. Borrajo is building both simultaneously.
What Comes Next
Amber Bio's initial disease focus is ophthalmology - specifically inherited retinal diseases - and CNS disorders. Both areas share the characteristics that make splice editing particularly relevant: high allelic diversity, serious unmet need, and patient communities that have been waiting for effective treatment options for a long time.
The Retinal Degeneration Fund's investment is a meaningful anchor for the ophthalmology work. The fund invests specifically in treatments for inherited retinal diseases, and their due diligence involves both scientific and patient-advocacy expertise. That combination of scientific validation and patient-community endorsement gives Amber Bio's ophthalmology program a particular kind of credibility.
Borrajo is also an active voice in the broader RNA editing field - speaking at the RNA Editing Summit, RNA Leaders Europe, and the Investival Showcase. He's not just running a company; he's helping define the category. In a field where platform differentiation matters enormously to investors and partners, that positioning work is part of the job.