The Gene Therapy Opportunity

The Gene Therapy Opportunity

Author | Source

Severin Renold

Weissknight Corporate Finance


BioTech, Gene Therapy

Blog only available in english


Market Overview


Serious diseases have traditionally been treated using drug therapy, which aims to manage the disease rather than cure it. More recently, advanced gene-therapy products, such as lentiviral vectors, have been used to permanently restore health to those suffering from severe disease.

  • Lentiviral vectors have been used to cure monogenic gene disorders by targeting bone marrow stem cells that give rise to mature immune cells. Conditions such as severe combined immunodeficiency (SCID), Hunter’s disease (and other storage disorders), Sickle Cell Disease (SCD), and Beta-Thalassemia are all primary examples.
  • Lentiviral vectors are the critical component of the revolution in the treatment of blood and other cancers, known as CAR-T cell therapy. Lentiviral vectors are used to modify white blood cells called T cells from the blood that then effectively recognize and kill the cancer cells in diseases such as leukaemia, lymphoma, and multiple myeloma. Kymriah®, Yescarta®, Tecartus®, Breyanzi®, Abemca®, and Carvykti® are all examples of FDA approved CAR-T cell products. There are a large number of CAR-T cell products in development requiring vector manufacturing services.


Digital Health

Understanding the Gene Therapy Opportunity

The basic idea of gene therapy is to introduce genetic material into cells to replace mutated genes or provide instructions to produce an advantageous protein.

How Gene Therapy works


For the gene of interest to reach the inside of the cell, it has to be packaged into a carrier vehicle. Mostly, these vehicles are viral vectors, but there are also non-viral carriers. Viral vectors are most often used as carriers because they can deliver the gene of interest with high efficiency using the natural mechanism for infecting cells. The viral vectors are engineered, so they are incapable of causing disease in humans. In gene therapy, the viral vector is composed of the capsid, the virus’s protein shell that carries the genetic material and envelope proteins that allow for binding and entry into the targeted cell.


  • The viral vector carrying the gene of interest enters the cell through the cell membrane. At this stage, the viral vector is packaged into a vesicle and transported to the cell’s nucleus. Here, the vesicle disintegrates, and the viral capsid disassembles, releasing the gene of interest into the cell’s nucleus through a nuclear pore.


  • Some viral vectors integrate the gene of interest directly into a chromosome once they enter the human cell’s nucleus. Other viral vectors, such as adeno-associated viral vectors, deliver their genes into the nucleus but do not integrate it into the cell’s genetic material.


  • Gene therapies can be delivered either in vivo – where the viral vector is injected or administered intravenously into the body – or ex vivo, where a patient’s cells are removed, the viral vector is then inserted into these cells outside of the body, and the cells containing the vector are reintroduced into the patient.


Gene Therapy Delivery Vehicles:


The inability of viruses to self-replicate unless they infect a living cell is a fundamental reason they have become so valuable for gene therapy development. In essence, viral vectors are modified viruses that contain the viruses‘ gene delivery skills while their pathogenic characteristics have been removed. A number of viral vectors have been developed to introduce genetic material into target cells. In gene therapy, the cargo can either replace a mutated, disease-causing gene with a healthy gene, inactivate an improperly functioning gene, or introduce a new gene into a patient’s body to help fight a disease. Today, there are four main viruses used as biotherapeutic vectors: retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses. Each of these viral vectors comes with its own limitations and advantages.


The 4 main viral vectors



A number of drawbacks associated with viral vectors have led to the study and development of non-viral vector solutions for gene therapy delivery into target cells or tissues. These drawbacks include manufacturing bottlenecks, upscaling challenges, cancer-causing mutations, and immunogenicity of viral vectors.

Non-viral administration methods can address a number of these limitations, especially those associated with safety. Synthetic gene therapy delivery vehicles, for example, usually have lower immunogenicity than viral vectors because patients will not have pre-existing immunity, which is the case with some viral vectors. Many non-viral vectors are also easier to manufacture and can deliver much larger genetic cargoes than some viral vectors.

Despite these advantages, very few of these non-viral vector solutions are actually used in the clinic, as they have their limitations. The main challenge currently facing non-viral vector solutions is the effective delivery of genetic material into mammalian cells due to many barriers, such as potential vehicle degradation before it can even reach the target cell.


Coronavirus and mask


Overview of the Market size & Potential

The Gene Therapy Market was estimated to be $ 4.2 billion in 2021 and is poised to grow at a CAGR of 26% by 2027 to reach $ 14.8 billion.

  • The COVID-19 pandemic is anticipated to have a positive effect on the gene therapy market. Gene and cell therapy technology are expected to be extensively used in the development of vaccines used to treat COVID-19.
  • The growth of this market is driven by the high incidence of cancer and other target diseases, the availability of reimbursements, and the increased funding for gene therapy research. However, the high cost of gene therapies is envisioned to hamper the market growth to a certain extent during the forecast period.


Investment in research and development (R&D) activities are also expected to have a significant effect on the market. Several companies aim to build a gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities and enhancing those capabilities through strategic collaborations, expansion of R&D movements, and potential licensing, merger, and acquisition activities.


Based on indication, the market is segmented into neurological diseases, cancer, hepatological diseases, Duchenne muscular dystrophy, and other symptoms.

  • The cancer segment is estimated to grow at the highest CAGR during the forecast period due to the approval of a growing number of gene therapies for cancer treatment and the rising incidence of hematologic cancers.
  • The cancer segment is anticipated to hold a significant share in the market. The factors bolstering the segment growth are the increasing burden of cancer disorder, the growing focus on research to develop an effective treatment for cancer, and rising investments pertaining to cancer research.
  • For instance, according to Globocan 2020, an estimated 19,292,789 new cancer cases and 9,958,133 deaths due to cancers were reported 2020 worldwide.
  • In the treatment of cancer, various gene therapy strategies are currently employed. These include anti-angiogenic gene therapy, pro-drug activating suicide gene therapy, gene therapy-based immune modulation, oncolytic virotherapy, correction/compensation of gene defects, antisense, genetic manipulation of apoptotic and tumor invasion pathways, and RNAi strategies.
  • The cancer types, such as brain, lung, breast, pancreatic, liver, colorectal, prostate, bladder, head and neck, skin, ovarian, and renal cancer, have been the target of these therapies.


The global gene therapy market is highly competitive and consists of a few major players. Companies like Amgen Inc., Bluebird Bio, Gilead Sciences, Inc., Novartis AG, Orchard Therapeutics, Sibiono GeneTech Co. Ltd., Spark Therapeutics (Roche AG), and UniQure N.V., among others, hold the substantial market share in the Gene Therapy market. They have various strategic alliances such as collaborations and acquisitions along with the launch of advanced products to secure their position in the global market.

In Europe, there are more than 300 biotech and pharma companies working in the gene therapy field, while there are over 600 in North America, according to GlobalData. A large number of small and medium-sized biotechs are developing gene therapies, and numerous big pharma companies are also working in the field, as mentioned earlier.


Genetic medicine


Overview of the Challenges

1) Challenges to realizing the potential of viral-vector gene therapies:

The current generation of viral-vector gene therapies represents the culmination of decades of biological and clinical research. As more patients have received these therapies, it has become clear that three fundamental challenges will restrict the applicability of viral vectors: getting past the immune system, lowering the dose, and controlling transgene expression. Ongoing work to address these challenges is generating technological innovations that have the potential to leapfrog current therapies and unlock the potential of viral vectors.

To tackle gene therapy hurdles, academic labs, start-ups, and established companies are generating various innovative solutions. Each focuses on a specific component of a gene-therapy product (for example, the viral capsid) or part of the development process (such as manufacturing). However, these creations often address considerable core challenges, outlining multiple paths to realizing the promise of viral-vector gene therapy.


Challenges in the gene therapy

Future trends:

  • Viral-vector gene therapies find themselves at another inflection point. Early successes in the treatment of rare diseases and blood cancers have proven the potential of this modality, while the challenges to gaining widespread adoption—the way that monoclonal antibodies have over the past 20 years—have only become more evident. Nevertheless, the wealth of inventive solutions being explored across academia, biotech, pharma, contract development, and manufacturing organizations demonstrates that viral-vector gene therapies are here to stay.


  • As described previously, different solutions are emerging to address each of the core challenges. The diversity of these approaches and the complexities of gene therapy means that no single process is likely to „win.“ That situation will enable a rapid creation cycle in which gene therapies are constantly being improved upon, which will offer new opportunities to leapfrog existing products.


  • Owners of viral-vector platforms will need to consistently look to the next set of innovations beyond their current platforms and assets. That could include investing directly to help overcome the broader challenges and buying or licensing critical technology to upgrade their outlets.




The manufacturing challenges:

As explained above, the early stages of gene therapy development involve continuous biophysical analyses and safety testing of the therapy’s viral and genetic components to ensure the safety and efficacy of the treatment when used in humans. However, challenges also pop up throughout different stages of the gene therapy manufacturing process.

  • A big challenge manufacturers face is the compressed timelines of gene therapy development. While the average result of a conventional biological takes between eight and ten years, gene therapy development takes three to five years.


  • These tight timelines also result in a number of other problems, including an increasing demand for plasmids – the critical building blocks for viral vector development – and growing bottlenecks in plasmid production; one of the reasons researchers are studying non-viral delivery methods for gene therapies


  • The increasing challenge of producing viral vectors at a large scale has forced many companies to think outside the box.


Another challenge related to process development is the fact that each disease and each target tissue requires a different dosage.

  • This complicates the production of standardized gene therapy development protocols.


  • At the same time, the growing popularity of gene therapy means the demand is outstripping the supply of expertise and manufacturing capacity. Here, gene therapy developers advocate moving manufacturing processes towards more automation and software solutions and handing the entire process to contract manufacturing organizations.


Moreover, a lack of optimized processes and fast testing is seen as one of the main drivers of the high costs of gene therapies. To address this problem, researchers are working on the development of new analytical methods like robust, fast, easy-to-use, and reproducible assays. These should be developed only for gene therapy assessment rather than being borrowed from traditional antibody development processes, as is currently the case.