Over the past several years, a resurgence of interest in gene-based medicine has spurred some industry watchers to speculate on the ultimate size of the market. Although the field is still in its relative infancy, its promise has led to a range of bullish estimates. For example, market research firm BCC Research forecasts the global market for DNA vaccines will grow at 54.8 percent compound annual growth rate (CAGR) to reach $2.7 billion by 2019, while two other observers, Roots Analysis and Research and Markets, both predict the gene therapy market as a whole to reach $10-11 billion by 2025. Meanwhile, a report from market intelligence firm Transparency Market Research forecasts that the global stem cells market will grow at a CAGR of 24.2 percent through 2018, and is bound to reach nearly $120 billion by the end of that period.

Are predictions like these realistic? While none of us has a crystal ball, we can get a better perspective on the market potential of this fast-developing field by taking a quick look at the broad spectrum of applications it encompasses, briefly touching upon some of the challenges that must be met if these strategies are to reach their full potential and advance through clinical testing and toward commercialization, and then quickly noting the versatility of some of the solutions currently available to bring gene-based medicine forward. 

Credit: GenVec, Inc.

The term “gene-based medicine,” broadly speaking, encompasses all of these treatment and prevention strategies:

  • cellular immunotherapy (such as CAR T-cells primed to react against various cancers)
  • gene editing (such the CRISPR/Cas system)
  • cell therapy (such as stem cells for a number of indications, including cancer, muscular dystrophy, Parkinson’s disease, etc.)
  • regenerative medicine (this can involve everything from artificial skin and cartilage to approaches for sensory restoration)
  • vaccines (here we mean vaccines that are not based on use of the entire viral or pathogenic organism, whether live attenuated or killed, but rather based on antigenic subunits of the target pathogen)
  • therapeutic gene delivery (what is sometimes thought of as the “classic” gene therapy approach—introduction of a corrective gene to replace a faulty or absent one either ex vivo or in vivo, to address a host of diseases, such as hemophilia, cystic fibrosis, etc. In addition, this category can also be thought of to deliver a gene/protein, which is a central player to the start of a biological function cascade that then provides the necessary clinical outcome)
  • nucleic acid therapeutics (this area includes everything from siRNAs and anti-sense oligonucleotides intended to silence disease-causing genes to introducing synthetic RNA into target cells to induce expression of a therapeutic or absent protein)
  • oncolytics (such as the use of modified viruses programmed to selectively target and lyse cancer cells)

Clearly, the range of diseases and conditions that can potentially be addressed through the sum of these approaches is enormous. Anyone in drug development knows that cutting-edge medicine must advance with caution and that the pathways to success are uneven.  So while the market size is extremely large when taken as a totality, it also comes as no surprise that the degree to which each of these approaches has advanced is different, or that each encounters its own challenges in the never-ending battle against pathogens, the diseases of aging, and genetic disorders. 

It would be infeasible to cover the challenges and developments in each of these arenas in one short piece. However, two of the big questions that must be answered to fully realize the potential of a number of these diverse efforts can be boiled down to just two small words: delivery and manufacturing.

To illustrate, let us briefly take a look at just one of the new approaches now under the gene-medicine umbrella— CAR T-Cell Therapy. 

The idea of the CAR T approach is to create an anti-cancer immune response by harvesting immune cells (T cells and sometimes also NK or natural killer cells) from the patient, growing them in cell cultures, and then transducing them with a chimeric antigen receptor (CAR) coding for specific tumor antigens or tumor cell surface molecules that will cause these lymphocytes to target tumors when reintroduced, thus “unmasking” cancer cells by depriving them of their greatest defense—the ability to pass as “self”— and exposing them to the body’s immune cascade rather than allowing them to evade it. 

When it comes to delivery, electroporation—using an electric pulse to force the CAR cassette into T cells in suspension—is one way of producing CAR T lots. The disadvantage of this approach is that, as it involves forcing the temporary opening of the cellular membrane, closure can be incomplete, the transfer of materials into and out of the cell during the process can be inexact, and/or an ion imbalance can be triggered in the cell, resulting in eventual cell death or dysfunction

Another, and more widely used, way of producing CAR T lots is transfection of the target T cells using either retroviral or lentiviral vectors bearing the CAR cassette. Lentiviruses, a subset of retroviruses, are currently the most frequently chosen vector because (like the most well-known of this viral group, HIV) they have a strong affinity for T cells and readily integrate into the host T-cell genome. Initial clinical results with difficult-to-treat cancers using CAR Ts prepared with these vectors have been promising. However, they do have certain potential disadvantages:

  • the potential for the appearance of replication-competent virus has kept manufacturing costs relatively high;
  • concerns over the potential appearance of recombinant replication-competent virus (i.e., new viral mutants) as result of exposure in patients to active wild-type viruses (for instance, HIV) persist; and
  • the fact that both retroviruses and their subset, lentiviruses, integrate permanently into the cellular host genome remains a long-term safety concern as this can trigger oncogenesis.

In addition, circulating CAR T cells have been shown to produce “on-target, off-tumor” toxicities that then have to be treated with immunosuppressive agents.

Viable alternative delivery and manufacturing approaches for CAR T strategies are available, however. Appropriately engineered adenovectors have been shown to result in high levels of immune cell transduction, including T and NK cells, while avoiding the possible drawbacks of electroporation as well as potential vector integration effects, since adenovectors do not integrate into the host cellular genome. In addition, adenovectors of rare human and non-human origins as well as proven cell lines are now available that can facilitate both high-level and sustainable transgene expression as well as allowing for well-defined, scalable and transferable replication-competent adenovirus (RCA) free manufacturing with high production yields, lowering the cost of goods. Last but not least, adenovectors can be used to introduce targeting moieties to minimize on-target, off-tumor side effects.

Overall, the optimism being expressed in some quarters regarding the market potential for gene-based medicine appears justified, particularly in view of the increased demand to address the diseases of aging, the unfortunate but also unsurprising emergence of new pathogens, as well as the constant need to stay a step ahead of the old disease enemies we already know. The impressive diversity of approaches being pioneered and the versatility of technology platforms to synergistically bring them to fruition suggest that the era in which the substantial field of gene-based medicines and vaccines matures and yields products is on the horizon—and that it is one bound to grow substantially in market value in years to come.   

About the Author

Douglas J. Swirsky is president and CEO of GenVec, Inc., a clinical-stage gene delivery company focused on developing a pipeline of cutting-edge therapeutics and vaccines using its proprietary AdenoVerse™ gene delivery and manufacturing platform.