Platform

Engineering by Design

CRISPR genetic medicines should be precisely engineered for therapeutic use

Discovery

Naturally occurring CRISPR systems have revolutionized genetic medicine since 2012, when their potential for gene editing was unlocked in the lab of our co-founder, Nobel Laureate Jennifer Doudna.

Challenges

These bacterial systems evolved to treat microbes, not humans. That’s why off-target effects and low activity are hurdles for many early CRISPR medicines.

Engineering by Design

CRISPR doesn’t have to be a shot in the dark. Scribe is rewriting genetic medicine by iteratively engineering CRISPR systems for greater potency and safety — so everyone can benefit.

Our initial CRISPR-based platforms, XE and ELXR, are highly engineered from natural  CRISPR enzymes for improved potency and safety

Using a novel, easy-to-deliver, and safer starting point — CasX — we’ve designed and engineered two platforms potent and safe enough to become standard of care for genetic medicines: XE for gene editing, and ELXR for epigenetic silencing.

A diagram showing the CRISPR gene editing process. At the top is a DNA double helix with a 'Target DNA Sequence' labeled. In the middle, a detailed molecular structure (likely Cas9) is shown interacting with the DNA, with labels for 'PAM', 'Engineered Guide RNA', and 'DNA cleavage' points. At the bottom, the resulting 'Edited DNA Sequence' is shown with a section highlighted in blue, indicating the edited region.
A diagram showing the CRISPR gene editing process. At the top is a DNA double helix with a 'Target DNA Sequence' labeled. In the middle, a detailed molecular structure (likely Cas9) is shown interacting with the DNA, with labels for 'PAM', 'Engineered Guide RNA', and 'DNA cleavage' points. At the bottom, the resulting 'Edited DNA Sequence' is shown with a section highlighted in blue, indicating the edited region.

Gene editing

X-Editor (XE)

Our X-Editor is highly diverged from naturally occuring CasX, with 100x improvements in activity and no detectable off-target editing.

Mechanism

Double-strand break (DSB) genome editing

Useful for

Knockouts (KO)

Knockdowns (KD)

Knockins (KI)

Knockups (KU)

Advantages

High potency in vivo

Allele specificity

Low to no off-target activity

Broad targeting versatility

Deliverability with all delivery systems

Well understood MOA and safety characterization

Strong, novel IP

An illustration of epigenetic regulation showing chromatin states. The top shows open chromatin with a 'Gene On' state and 'Target DNA in Open Chromatin.' The middle shows a molecular complex labeled with 'EPI-Marking.' The bottom shows condensed chromatin with multiple histone proteins, labeled as 'EPI-Represses DNA Sequence' and 'Gene Off.' White circles represent histones, and the DNA double helix is shown threading through these structures. The active state is marked in blue while the repressed state is marked in red.
An illustration of epigenetic regulation showing chromatin states. The top shows open chromatin with a 'Gene On' state and 'Target DNA in Open Chromatin.' The middle shows a molecular complex labeled with 'EPI-Marking.' The bottom shows condensed chromatin with multiple histone proteins, labeled as 'EPI-Represses DNA Sequence' and 'Gene Off.' White circles represent histones, and the DNA double helix is shown threading through these structures. The active state is marked in blue while the repressed state is marked in red.

Epigenetic editing

Epigenetic Long-Term X-Repressor (ELXR)

ELXR is designed to turn off gene expression of multiple genetic targets without cutting DNA.

Mechanism

Non-permanent epigenetic marking of DNA and chromatin

Useful for

Durable and complete gene silencing

Gene tuning

Multi-gene repression

Reversible gene silencing

Advantages

High potency

Specificity

Reversibility

Multiplex gene silencing

Intrinsic safety advantages of non-permanent editing

Strong, novel IP

How it works

Stepwise molecular engineering transforms natural CRISPR systems into medicines for broad patient populations.

01

Chart the destination

Surgeons don’t use just any tool for surgery – they use purpose-designed and built scalpels. This should be true for the tools we use for genetic surgery. But the CRISPR systems of today are mostly unrefined and unoptimized for the human genome.

We’re engineering CRISPR tools to be like the fine scalpels of modern surgery. To do that, we start by setting precise therapeutic objectives, focusing on the specific characteristics needed for safe and effective CRISPR-based medicines. This stage guides our entire process, defining what “success” looks like in terms of activity, specificity, deliverability, and more.

Our Portfolio
02

Start at the start

We select a foundational molecule that aligns most closely with our goals. Our starting points all have highly differentiated intellectual property.

03

Map the landscape

We create thousands to millions of mutations on our base molecule, each representing a potential improvement. We experimentally test these variants for our target characteristics, providing a local map of our fitness landscape.

04

Take the next step

We identify the variant that performs best for our current fitness goal, taking an intentional “step” on our landscape.

05

Repeat, repeat, repeat

We reapply the mutation and screening process, step by step, to continually improve our CRISPR system. This iterative journey up the fitness landscape enables us to optimize one characteristic at a time, or multiple features in parallel with screens adjusted to assess multiple therapeutic characteristics.

06

Holistic engineering

We leverage this process to optimize beyond the CRISPR enzyme itself but the entire therapeutic package, including the guide RNA and delivery systems. Each component is engineered holistically to create a finely tailored therapeutic.

Our process enables the creation of CRISPR tools and platforms with strategic advantages in safety and specificity, potency, targeting range, and delivery. Ultimately, this leads to better genetic medicines capable of improving health outcomes for the many.

Scribe has developed a next-generation platform for CRISPR-based therapeutics that will fundamentally transform how we will diagnose, treat, and manage disease at scale. The company represents a shift in therapeutics, from a slow discovery-based approach to fully industrialized, engineered medicine, which will unlock the rapid development of novel therapeutics to improve the lives of millions of people worldwide.

Vijay Pande

Andreesen Horowitz, General Partner

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