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Cell and Gene Therapy 101: A Primer on Advanced Therapies

What if instead of treating the symptoms of a disease, we could target the source of the disease itself? Cell and Gene Therapy (C&GT) can do just that. These advanced therapies are the result of decades of research on the building blocks (cells) and blueprints (genes) of human biology. This burgeoning field of science and medicine has great potential for treating and curing genetic diseases and cancer. While most C&GT is considered next-generation therapy, some forms of C&GT are already improving the lives of patients.


In this primer, we explore the essential aspects of C&GT: what it is, the current state of business, the potential for the future, and the remaining challenges.


Background and Outlook

Scientists built the foundation for C&GT and now technology has caught up with the science. In the last decade, genetic sequencing and cloud computing both became faster and less expensive. Now, computational power and genome sequencing are accessible to the scientific and medical community. These technological advances are enabling a new era of scientific discovery (see Synbio 101 and Proteomics 101 to learn more about how we got here).


According to the FDA, “Cell and gene therapy-related research and development in the United States continue to grow at a fast rate, with a number of products advancing in clinical development.” Here are a few compelling reasons to pay attention to C&GT right now:

  • The U.S. Food and Drug Administration (FDA) has approved 22 C&GT therapies so far. And there are thousands of clinical trials underway.

  • The global C&GT market reached a value of nearly $4.4 billion in 2020, having increased at a compound annual growth rate (CAGR) of 25.5% since 2015, Yahoo reports.

  • The market is expected to grow at a rate of 28.7% to reach $15.5 billion in 2025 and a CAGR of 17.3% from 2025 and reach $34.3 billion in 2030.


Defining Cell and Gene Therapies

Both advanced therapies are related and often discussed together but they are distinct approaches to treat or cure diseases.


Gene Therapy

Gene therapy uses a vector (in other words, a vehicle or carrier, such as an inactivated virus) to deliver a gene, DNA or RNA. Genes encode for proteins, and gene therapy ensures that the right proteins are being encoded. So instead of fixing the symptom of the disease, gene therapy goes straight to the cause of the disease and tries to fix it.


Most gene therapy does one of 3 things:

  • Replaces a mutated gene that causes disease with a healthy copy of the gene.

  • Inactivates, or “knocks out,” a mutated gene that is functioning improperly.

  • Introduces a new gene into the body to help treat a disease

The key challenges with gene therapy are:

  • Delivery of the vector (usually, an inactivated virus that has been genetically engineered to deliver a gene)

  • Limitations on the size of the gene that you can insert into a vector

Looking ahead, the next generation of gene therapy uses novel approaches such as non-viral vectors like synthetic DNA.


Cell Therapy

In cell therapy, the cell itself is the therapy. There are two main types of cell therapies: allogeneic therapies, which come from donor tissues, and autologous therapies, in which the cells come from the patient.


In some cases, both cell and gene therapy combine, such as treatments that involve removing a patient’s stem cells, modifying them to express a new gene, and then returning the modified cells to the patient’s body to treat disease.


Potential

The fundamental principles behind C&GT are well established.


Scientific American points out that basic gene therapy, such as the ability to add a corrected gene into the genome, has been available for a while. Gene therapies have been approved to treat: certain types of skin cancer, blood disorders, and rare genetic diseases. Cellular therapies, such as CAR-T therapy for treating lymphoma, have been researched since the 1960s and approved since 2017.


Cell and Gene Therapies are especially poised to treat:

  • Spinal Muscular Atrophy

  • Sickle Cell Disease

  • Blood cancer

  • Liver diseases

  • Cystic fibrosis

  • Heart disease

  • Diabetes

  • Hemophilia

  • AIDS

And now we are seeing the next generation of cell and gene therapy, thanks to advances in the last decade. In 2012, the introduction of the gene-editing tool called CRISPR, known as molecular scissors, helped push C&GT out of the lab and into the real world. This tool is so transformative and holds such great potential that its inventors, Doctors Jennifer Doudna and Emmanuelle Charpentier, were awarded the 2020 Nobel Prize in chemistry. Today, C&GT breakthroughs are leading to even more breakthroughs.


As recently as June 2021, researchers announced that CRISPR injected into the blood treated a genetic disease for the first time. They injected a CRISPR therapeutic into people who were born with a fatal nerve and heart disease. In three of these patients, the injection nearly shut off the production of a toxic protein.


Challenges with Advanced Therapies

In both cell and gene therapies, there is a plethora of research that shows how they will work theoretically. So, what’s the catch? C&GT experts are still refining the process.


“There are nuanced challenges for cell therapies and gene therapies,” says Geoffrey Glass, CEO of Kiniciti, a firm investing in companies that play essential roles in supporting the development and manufacturing of Cell and Gene Therapies.


Extensive research has been done over recent decades to ensure the safety and efficacy of C&GT, and additional research continues at a rapid pace. It is especially important to avoid any “off target” effects, such as unintentionally affecting cells that you aren’t targeting or overdosing the delivery vectors, which could trigger an immune response that could potentially negatively impact patients.


As a 30-year veteran of the life sciences industry, Glass sees great potential for C&GT once the process challenges are solved. He explains that while traditional drug development focuses on finding molecules and then reproducing them, C&GT faces an entirely different dilemma: How to make and deliver these advanced therapies reliably at scale.


“In this space, it's less about the clinical study design,” he says. “It's more about figuring out your process, characterizing your process, making sure it's pure, and how you introduce it to the human body.”

Pioneers in C&GT like Glass and his colleagues are tackling different challenges for each type of advanced therapy.


In gene therapy, the most challenging aspect is figuring out the exact details of the delivery vehicle (vector) that will safely pass along instructions to the body, such as removing, editing, or replacing a gene of interest.


For cell therapies, the trick is reducing variation in the process. For example, in allogeneic therapies (when the cells come from someone else), Glass says, “If you can't go back to the same donor patients to get the same cells, you end up with variation in your process.”


And even with autologous therapies (when the cells come from the patient), the logistics of harvesting and preserving the cells is a complex process with a delicate and costly supply chain.


“The challenge is us,” Glass says. “The human body is the most complex system that there is and this is all about how do you deliver, either the cells, the edits, or the engineering, to the right location with the right quantity, the right specificity. It's what I call a Process-Science Challenge.”