Gene therapy transformed the world. Now we seek to transform gene therapy.

Imagine a world 
not limited by genetic disease.
Envisioning a future where people everywhere live free from the devastation of genetic disease.
When one or more genes in a person’s DNA is missing or mutated, it can cause a genetic disease, progressively damaging the body over time. Gene therapy works by introducing normal, functional copies of the missing or mutated gene into the cells of a patient to treat a specific disease.

Current gene therapies use a viral delivery vehicle (vector) to carry the functional gene into the body and access the cell nucleus where it works. The most commonly used vector is adeno-associated virus (AAV). While AAV gene therapy has been a great advancement, it also has constraints. Due to limitations in the size of gene it can carry and the inability to manufacture large amounts, AAV therapy is currently limited to rare diseases. Also, patients can only be given a single dose, so if efficacy begins to wane over time, they cannot be redosed to maintain benefit. And up to half of patients are not eligible for AAV therapy due to pre-existing natural immunity to the virus.

At Generation Bio, our platform, comprised of our ceDNA construct, our ctLNP delivery system and our scalable capsid-free manufacturing process, is designed to overcome the limitations of current gene therapy approaches. Our mission is to create an entirely new class of non-viral gene therapy that leaves no patient behind, providing long-term efficacy, while offering the ability to redose if needed, treating a wide range of both rare and prevalent diseases.

Our mission isn’t easy, and we’re okay with that.
When one or more genes in a person’s DNA is missing or mutated, it can cause a genetic disease, progressively damaging the body over time. Gene therapy works by introducing normal, functional copies of the missing or mutated gene into the cells of a patient to treat a specific disease.

Current gene therapies use a viral delivery vehicle (vector) to carry the functional gene into the body and access the cell nucleus where it works. The most commonly used vector is adeno-associated virus (AAV). While AAV gene therapy has been a great advancement, it also has constraints. Due to limitations in the size of gene it can carry and the inability to manufacture large amounts, AAV therapy is currently limited to rare diseases. Also, patients can only be given a single dose, so if efficacy begins to wane over time, they cannot be redosed to maintain benefit. And up to half of patients are not eligible for AAV therapy due to pre-existing natural immunity to the virus.

At Generation Bio, our platform, comprised of our ceDNA construct, our ctLNP delivery system and our scalable capsid-free manufacturing process, is designed to overcome the limitations of current gene therapy approaches. Our mission is to create an entirely new class of non-viral gene therapy that leaves no patient behind, providing long-term efficacy, while offering the ability to redose if needed, treating a wide range of both rare and prevalent diseases.
Our proprietary non-viral gene therapy platform
Three breakthroughs in construct, delivery and manufacturing empower our mission to create a new class of scalable, redosable, non-viral gene therapy for millions of patients living with rare and prevalent diseases.
BROAD THERAPEUTIC REACH.
Our closed-ended DNA construct has far-reaching possibilities.
Different genetic diseases involve different sized genes. Our closed-ended DNA construct (ceDNA, pronounced sed-na) has almost three times the capacity of AAV capsids, enabling it to carry large, and even multiple, genes to a cell. With this ability, ceDNA could allow us to treat a wider range of rare and prevalent diseases than what is currently possible with viral gene therapy. Further, ceDNA has the potential to offer durable expression, which means one treatment could last years.
Take a deeper dive
into ceDNA.
BROAD THERAPEUTIC REACH.
Our closed-ended DNA construct has far-reaching possibilities.
Different genetic diseases involve different sized genes. Our closed-ended DNA construct (ceDNA, pronounced sed-na) has almost three times the capacity of AAV capsids, enabling it to carry large, and even multiple, genes to a cell. With this ability, ceDNA could allow us to treat a wider range of rare and prevalent diseases than what is currently possible. Further, ceDNA has the potential to offer durable expression, which means one treatment could last years.
Take a deeper dive
into ceDNA.
Different genetic diseases involve different sized genes. Our closed-ended DNA construct (ceDNA, pronounced sed-na) has almost three times the capacity of AAV capsids, enabling it to carry large, and even multiple, genes to a cell. With this ability, ceDNA could allow us to treat a wider range of rare and prevalent diseases than what is currently possible with viral gene therapy. Further, ceDNA has the potential to offer durable expression, which means one treatment could last years.
Let's start at the beginning. Literally.
We are focused on creating a new class of non-viral gene therapy that will allow treatment in infancy, before a genetic disease has a chance to progress. We see a future where people live long, full lives never realizing how their genetic conditions could have once affected them.
REDOSABLE. TITRATABLE.
By changing the way gene therapy is delivered, we’re changing what’s possible.
In order to do its important work, our ceDNA has to carry a gene or genes to the right location in the body and access the cell’s nucleus. For this, we’ve engineered our cell-targeted lipid nanoparticle (ctLNP). Being non-viral, this delivery system can be available to everyone, and unlike viral gene therapy, does not exclude patients with preexisting immunity. Further, since our ctLNP has been designed to avoid activation of the immune system upon initial dose, a patient’s treatment can be titrated in steps to achieve the right individual outcome, without overshooting, and redosed if needed to extend the effect of treatment over a lifetime.
Take a deeper dive
into ctLNP.
REDOSABLE. TITRATABLE.
By changing the way gene therapy is delivered, we’re changing what’s possible.
In order to do its important work, our ceDNA has to carry a gene or genes to the right location in the body and access the cell’s nucleus. For this, we’ve engineered our cell-targeted lipid nanoparticle (ctLNP). Being non-viral, this delivery system can be available to everyone, and unlike viral gene therapy, does not exclude patients with preexisting immunity. Further, since our ctLNP has been designed to avoid activation of the immune system upon initial dose, a patient’s treatment can be titrated in steps to achieve the right individual outcome, without overshooting, and redosed if needed to extend the effect of treatment over a lifetime.
Take a deeper dive
into ctLNP.
In order to do its important work, our ceDNA has to carry a gene or genes to the right location in the body and access the cell’s nucleus. For this, we’ve engineered our cell-targeted lipid nanoparticle (ctLNP). Being non-viral, this delivery system can be available to everyone, and does not disqualify patients with preexisting immunity.

Further, since our ctLNP has been designed to avoid activation of the immune system upon initial dose, a patient’s treatment can be titrated in steps to achieve the right individual outcome, without overshooting, and if needed, re-dosed to extend the effect of treatment over a lifetime.
Genetic disease is a family thing.
When genetic disease touches a life, it affects a whole family. We look to the day when parents, grandparents, brothers, sisters and spouses can spend less time focused on their loved one’s health and more time enjoying their loved one’s life.
Global potential.
If you can efficiently manufacture millions of doses you can effectively change millions of lives.
Our goal to create a new class of non-viral gene therapy that leaves no patient behind calls for a manufacturing process that is reliable and scalable. Our capsid-free manufacturing process is engineered to use existing biologics facilities to enable not thousands, but millions of doses. We seek to create unprecedented access for patients everywhere. Together with our large-capacity ceDNA and our non-viral ctLNP delivery system, our scalable manufacturing enables our vision: a future where gene therapy is available to more people living with more diseases, in more places around the world.
Take a deeper dive
into capsid-free manufacturing.
Global potential.
If you can efficiently manufacture millions of doses you can effectively change millions of lives.
Our goal to create a new class of non-viral gene therapy that leaves no patient behind calls for a manufacturing process that is reliable and scalable. Our capsid-free manufacturing process is engineered to use existing biologics facilities to enable not thousands, but millions of doses. We seek to create unprecedented access for patients everywhere. Together with our large-capacity ceDNA and our non-viral ctLNP delivery system, our scalable manufacturing enables our vision: a future where gene therapy is available to more people living with more diseases, in more places around the world.
Take a deeper dive
into capsid-free manufacturing.
Our goal to create a new class of genetic medicine that leaves no one behind calls for a manufacturing process that is reliable and scalable. Our capsid-free manufacturing process is engineered to use existing biologics facilities to enable not thousands, but millions of doses. We seek to create unprecedented access for patients everywhere.

Together with our large-capacity ceDNA and our non-viral ctLNP delivery system, we envision a future where genetic medicine is available to more people living with more diseases, in more places around the world.
Unlocking the potential of genetic medicine and the potential of Zac and Jonathan
Zac and Jonathan were born with a rare genetic disease called phenylketonuria, or PKU, that severely restricts their diets. Their big, loving family spends every dinnertime laughing around the same long dining table, even if they have to eat very different foods.
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Novel Structure
Our high-capacity ceDNA is an engineered, double-stranded, linear, covalently closed-ended DNA construct that includes the gene of interest and other regulatory elements that drive expression. This genetic payload is flanked by two inverted terminal repeat (ITR) sequences which are responsible for many of ceDNA’s unique features.
Native Gene Regulation
The large capacity of our ceDNA constructs provides us the freedom to incorporate native regulatory elements naturally associated with the gene we are replacing. These regulatory elements act as powerful “on/off” switches which may enable expression of the therapeutic protein to adjust in response to changes in the patient’s body.
LARGE PAYLOAD CAPACITY. 
NEW INDICATIONS.
ceDNA has significant payload capacity that can deliver constructs of 12 kilobases, almost three times the capacity of AAV. This increased capacity creates the opportunity to treat diseases caused by larger genes such as Wilson disease, LCA10 and Stargardt disease. It also allows for the potential to include novel multi-gene constructs to produce complex biologics such as monoclonal antibodies and to address conditions that need more than one type of genetic correction.
MORE POTENT CONSTRUCTS
Our large capacity ceDNA constructs have the potential to utilize novel expression elements that exceed the capacity of currently available gene therapy modalities. This may enable improved expression to treat diseases such as hemophilia A and Gaucher disease and potentially lower the dose required to achieve therapeutic efficacy.
Durable Expression
Once in the host cell nucleus, ceDNA drives durable expression of the gene of interest without integrating into the genomic DNA. This durability has the potential to enable years-long expression with each dose, minimizing the treatment burden for patients.
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ABILITY TO REACH PEDIATRIC PATIENTS
Children grow fast, and their cells divide rapidly. This is a challenge for traditional, viral-based gene therapy because the effect of the treatment “washes out” over time as cells divide. The ability to titrate the initial doses of our ceDNA-ctLNP may offer infants and children appropriate levels of treatment when it matters most – before disease progression is underway — and the ability to redose if needed may allow our therapies to extend expression throughout life.
INDIVIDUALIZED PATIENT TITRATION
Unlike the vectors used to deliver viral-based gene therapy, our non-viral ctLNP delivery system has been designed to avoid activation of the immune system in patients upon initial dose. This enables individualized patient titration whereby each patient can be redosed until they reach the expression level required to address their specific therapeutic needs.
LIFELONG IMPACT
We expect our gene therapies to have a durable effect, enabling years long expression for patients with each dose, similar to current viral-based gene therapies. If expression of the gene of interest begins to wane over time, the ability to redose our ceDNA-ctLNP may restore effective expression levels, prolonging the benefits of our therapies throughout a patient’s life.
GREATER OPPORTUNITIES FOR HUMAN TRIALS
With the ability to titrate and redose, we believe that a greater proportion of patients participating in our early clinical trials may achieve the desired level of gene expression.
TARGETED, MULTI-TISSUE DELIVERY
Our ctLNP uniquely employs biological ligands designed to engage receptors on the surface of specific tissues, such as the liver or the muscle. We aim to deliver ceDNA to the exact tissue where it’s needed, with limited delivery to off-target cells. We believe this will improve the safety and efficacy of our products. Because the system is modular, we can exchange ligands to reach different tissues as needed for different diseases.
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TARGETING RARE AND PREVALENT DISEASE
There are approximately 5000 rare diseases and more than a million common ones. We see the capacity to scale to millions of doses offering the ability to treat not only rare diseases, but prevalent ones, as well. This is a new frontier for gene therapy, with the goal of leaving no patient behind.
GLOBAL POTENTIAL
With our highly scalable, cost-effective manufacturing process, we aim to make gene therapy available for more people, for more diseases, in more places around the world. We are focused not just on rare diseases, but also on prevalent ones affecting millions of patients globally. Our goal is to leave no patient behind.
POTENTIAL TO SCALE FOR WORLDWIDE ACCESS
We engineered our process to use a system that takes advantage of 8 decades of biologics manufacturing experience. We’ve successfully completed manufacturing runs up to 200L of ceDNA drug substance using existing biologics infrastructure. With this, we expect to be able to efficiently scale to millions of doses, potentially enabling worldwide access to our gene therapies.
HIGH QUALITY
Our ceDNA drug substance is harvested from cells and purified before being encapsulated in ctLNP to create the final drug product. This allows for a highly pure product and greater control compared to current viral gene therapy approaches. With the process and controls we have developed to purify ceDNA, we consistently achieve greater than 99% ceDNA purity.

Take a seat at the table.

We are always looking for those who are ready to share their vision, talent, and tenacity—who believe in our mission and themselves.

Imagine a world without genetic disease.

What do you see? More health? Fewer doctor appointments? More bike riding? More peanut butter and jelly sandwiches? More life?
See our shared vision.
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