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The Ensoma Engine

Our ingeniously engineered Engenious™ vectors are versatile and precise, extending the reach of genomic medicine and cell therapy for rare and broad diseases.

Our Approach

What if we could deliver, in a single injection, effective treatments to patients without the need for myeloablative conditioning, stem cell collection or ex vivo cell modification in outpatient settings or other areas where access to sophisticated healthcare systems or specialty centers may be limited?

The foundation of Ensoma’s next-generation approach is our ingeniously engineered Engenious™ vectors. Also known as helper-dependent adenoviral vectors or “gutless vectors,” our Engenious vectors are designed to deliver a diverse range of gene modification technologies – including those that require a high level of packaging capacity – directly to blood stem cells, also known as hematopoietic stem cells (HSCs), or the various types of cells that arise from these cells, such as T cells, B cells and myeloid cells, without the need for stem cell collection or prior conditioning (e.g. chemotherapy).

Engenious™ Vectors

The versatility of Ensoma’s Engenious vectors allow precision engineering of various cell types, addressing a broad range of diseases.

At Ensoma, we have engineered our vectors – which are based on two decades of foundational academic and clinical research – so they are devoid of any viral genes.

This minimizes the chance for an immune response and frees up ample storage space to deliver a diverse range of gene modification technologies, or therapeutic cargo, which include:

  • Genome editing approaches
  • Targeted and random genomic integration methods
  • Regulatory elements for cell type-specific gene expression

These approaches enable Engenious™ vectors to modify various erythroid, lymphoid (e.g., T cells, B cells) and myeloid (e.g., macrophages, microglia) cell types, with great precision and vast therapeutic potential. Addressable indications range from rare monogenic diseases to broader diseases such as oncology, autoimmunity and infectious diseases via precision, off-the-shelf engineering of the immune system.

Our Engenious™ Vectors

Our Engenious™ vectors allow for up to 35 kilobases (kb) of packaged DNA — a very high capacity compared to <10 kb for vectors used for current ex vivo and AAV gene therapies.

Engenious
vectors
Other Vectors
High packaging capacity
Compatible with all gene modification tools
Preferential HSC targeting
Low likelihood for immune response
Precise titration to therapeutic levels
One-time treatment
Conditioning not required
Stem cell collection not required
Redosing not required

Given the highly specific nature of these technologies, we are able to preferentially target HSCs, as well as the various types of cells that arise from stem cells – including T cells, B cells and myeloid cells – inside the body. 

Another benefit of our vectors being devoid of viral genetic coding is low immunogenicity. When coupled with low population seroprevalence associated with the vector capsid, preexisting immunity in patients is unlikely. Once inside the body, our vectors are able to circulate in the bloodstream and effectively deliver therapeutic cargo to target cells to serve as a new set of instructions.

How it works

1. Mobilization

Draw HSCs out of the bone marrow

2. Transduction

Delivery of therapeutic cargo

3. Selection

Selective repopulation of edited
HSCs in bone marrow

We’ve engineered our in vivo therapies in such a way that edited cells have what’s called selective advantage.

Over time, it is these cells that proliferate in the bone marrow and initiate healing of the body from within.

Additionally, our proprietary approach allows us to precisely titrate the level of benefit to lasting therapeutic levels without the need to re-dose patients with our vectors, bypassing the immunogenic challenges associated with re-dosing required by other gene therapy modalities. 

Challenges of Bone Marrow Transplants And Cell Therapies

Patients undergoing bone marrow transplants or cell therapy treatments require access to extensive medical infrastructure and sometimes require lengthy stays in the hospital until they recover.

In both cases, patients require what’s called conditioning prior to treatment. Conditioning is necessary to make space in the bone marrow for the donor cells to engraft, as well as to suppress the patient’s immune system to lessen the chance of graft rejection.

Challenges with Current Gene and Cell Therapies

Approaches used in ex vivo gene and cell therapies often require that patients undergo conditioning with high levels of chemotherapeutic agents to ablate the bone marrow, which facilitates engraftment of the modified cells.

Further, patients are then infused with the modified cells after a slow and costly manufacturing process. Access to these therapies is highly limited with patients required to travel to specialized treatment centers.

ENSOMA’S IN VIVO APPROACHOTHER APPROACHES
ConditioningNoneRequired
Stem Cell CollectionNoneRequired
Manufacturing
Off-the-shelfComplex
ProcedureOut-patientIn-patient
AccessBroadLimited

In other words, our therapies are designed to be portable and accessible by people everywhere, including settings where access to healthcare systems or specialty centers may be limited.

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Recent Publications

In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model