LISBON, Portugal – Nerai Bioscience, a biotechnology company spun out from the University of Zurich and ETH Zurich, is working to make gene editing therapies more efficient, more precise, and scalable for rare disease patients. By combining artificial
intelligence, high-throughput protein engineering, and CRISPR-based editing, they can address multiple rare genetic diseases through a single technological platform.
CRISPR history
In 2020, Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize
in Chemistry for transforming a bacterial immune mechanism into a programmable
genome editing tool, laying the foundation for modern CRISPR-based therapies.
CRISPR originated as an adaptive immune system in bacteria, where fragments of viral
DNA are stored in the genome and transcribed into guide RNAs that direct nucleases
such as Cas9 to recognize and cleave matching viral sequences. To do this, Cas9 must
first find a short DNA motif called PAM (protospacer adjacent motif) next to the target
site. “PAM sequences are ubiquitous in the genome and act as a required ‘landing pad’ for
Cas9”, explained Vincent Forster, CEO of Nerai Bioscience. “While this enables CRISPR to permanently correct some genetic defects in human cells, it also carries the risk of unwanted gene edits, which have raised concerns about long-term safety, including cancer risk. So, we engineered a safer solution from the ground up”.
What Makes Nerai’s Approach Unique?
“Unlike other CRISPR approaches, Nerai engineers bespoke Cas9 editors tailored to
new and specific PAM sequences rather than using one-size-fits-most constructs that
typically induce more unwanted off-target edits.”
Forster explained to CheckOrphan that “This allows us to significantly expand the
number of genetic targets that can be edited while improving precision”.
Nerai’s cutting edge platform can thus treat more rare diseases, while essentially
eliminating unwanted side effects from incorrect DNA edits.
Nerai Pilot Project: Citrullinemia type 1
Nerai’s lead therapy targets a life-threatening pediatric ultra-rare disease, called
Citrullinemia type 1 (CTLN1). CTLN1 is a metabolic disorder caused by mutations in the ASS1 gene. This mutation produces a defective ASS1 enzyme, which leads to the accumulation of ammonia in the blood and brain, or hyperammonemia.
Hyperammonemia is highly neurotoxic, particularly in newborns. Without rapid
intervention, the disease can lead to severe and permanent brain damage or death.
The current standard of care relies on strict dietary protein restriction and ammonia
scavenger drugs; however patients experience recurrent metabolic crises and
hospitalizations, which ultimately require a liver transplantation.
The disease affects approximately 100 newborns per year across the US and Europe,
with a single mutation (c. 1168G>A) accounting for a large proportion of cases.
“We selected this rare disease because it sits at the intersection of high clinical need,
strong regulatory tailwinds, and a collaboration with a world-class clinical site in Zurich”,
explained Forster “It made this the perfect anchor indication to bring our platform to patients”.
Benchmark
Recent clinical experience has shown just how quickly CRISPR-based therapies can
move from concept to patient in urgent settings. In a similar pediatric metabolic disease
(CPS1), a personalized gene editing treatment was developed and delivered in less
than a year, with encouraging early outcomes.
While such one-off approaches remain complex to scale, they provide strong validation
of both the speed and therapeutic potential of this technology.
Regulators understand this potential. In February 2026, the FDA introduced the
Plausible Mechanism Framework, which allows clinical evidence from one approved
gene editing therapy to support the approval of product variations targeting other
mutations, without requiring a separate clinical trial for each one.
This principle aligns directly with Nerai’s platform strategy: a single validated editor,
reusable across specific mutations by swapping only the guide RNA.
Nerai’s ambition is to build on this momentum by making precision gene editing more
standardized and accessible for a broader group of rare disease patients.
Next Steps
Nerai’s lead compound NB-301 efficiently corrects the most common mutation
associated with CTLN1. NB-301 is delivered to the liver via lipid nanoparticles (LNP) and in vivo studies have demonstrated a mutation correction efficiency in hepatocytes well above the estimated threshold needed for clinical benefit.
Now, Nerai is advancing toward proof-of-concept studies in a mouse model that closely
replicates the genotype and phenotype of human citrullinemia type 1.
NB-301’s clinical development is centered on world-leading clinical centers with wide
access to patients, such as the UCD Translational Center at Children's Hospital Zurich.
With rare disease therapies increasingly commanding premium pricing and benefiting
from regulatory incentives such as priority review vouchers, Nerai’s business model has
the potential to generate significant value across multiple indications.
Following CTLN1, Nerai plans to expand its gene editing therapy to additional metabolic
diseases in a cost-efficient manner, by re-using the core components – the editor and
the LNP – and simply swapping the guide RNA that directs the editor to the target
mutation.
Nerai’s Vision
By bridging cutting-edge genome engineering with a scalable development strategy,
Nerai aims to redefine how rare disease therapies are discovered, developed, and
delivered.
As Forster emphasized, “The goal is not only to cure individual diseases but to build a
system where no genetic condition is too rare to be addressed.”
For more information, contact:
Vincent Forster