Genetic Engineering

Making gene editing therapies a commercial reality.
BlogFebruary 18, 2023

Delivering Genetic Editing Therapies to Market

In the past 10 years, our understanding of molecular biology and genetic engineering has continued to expand. Breakthrough approaches in gene editing are revolutionizing therapeutic research, with the first CRISPR-based treatment set to apply for regulatory approval by the end of 20221.

In this blog, Dr. Rajiv Vaidya, Head of Manufacturing Science & Technology (MS&T) and Dr. Samir Acharya, Associate Director of Process Development provide their unique insight into the steps necessary to allow commercially available gene editing therapeutics to become a reality.


Enhancing Therapies with Gene Editing

There are over 10,000 known human disorders caused by single gene mutations and despite being relatively rare, these genetic disorders are thought to affect around 1% of the global population1. In the last decade, innovations have enabled the development of genetic engineering technologies capable of inserting, deleting, modifying, or replacing DNA to overcome the effects of genetic abnormalities. These revolutionary new gene editing technologies include:


CRISPR-Cas machinery can be used to specifically target particular DNA sequences and make a double-stranded cut. Depending on the CRISPR-Cas tool being used, the target gene can be inactivated during repair, or the genes can be manipulated to add new DNA segments or edit single nucleotides.

Zinc finger nucleases (ZFNs)

Like CRISPR-Cas technologies, ZFNs act to create double-stranded breaks in DNA at specified locations. The zinc finger domains of ZFNs recognize and bind to specific DNA sequences, effectively delivering and directing the nuclease component to the desired cut site. The cell’s natural DNA-repair processes are then stimulated and harnessed to generate precise edits at the target site.

As these molecular tools have advanced, their capabilities have inspired biopharma developers and researchers to broaden their use into various therapeutic areas, from cancers to motor neuron disorders2,3.


Making Genetic Editing a Reality

Effective editing of patient genes not only relies on the controlled and precise alteration of DNA by technologies like ZFNs or CRISPR-Cas, but the delivery of the editing machinery to the target cell. Delivery poses its own challenges, requiring:

  • Protection of the genetic material encoding the editing machinery throughout its journey from the administration site to the target
  • Specific recognition of specific target tissues or cell types
  • Insertion of the editing machinery genes into target cells.

Considering these requirements, gene editing therapy developers are looking towards viral vectors like adeno-associated virus (AAV) and lentivirus (LV) as potential delivery vehicles. With the ability to carry relatively large cassettes, viral vectors could be used to transport genetic material encoding the gene editing machinery to specific target tissues and cell types. Utilizing certain serotypes and pseudotyping could further help refine the viral vectors’ tropism and enhance target cell specificity. Viral vectors like AAV are also considered to be poorly immunogenic, enabling the protection of genetic cargo from destruction by the host immune system.


Overcoming Challenges on the Path to Commercial Availability

For revolutionary gene editing therapies to change the lives of patients, developers and manufacturers will need to overcome the challenges on the path to clinical and commercial production.

Ensuring patient safety

As with all therapies introducing or modifying genetic material within patient cells, safety should be of the utmost importance. Risks stemming from off-target interactions, uncontrolled recombination events, or immunogenicity must be considered and minimized.

Preventing risk will not only require a strong understanding of the function and activity of gene editing machinery but also the delivery vehicle. A high level of expertise in viral vector development will be needed to carefully design vectors to prevent off-target delivery and immunogenic reactions. Manufacturing processes must be optimized to enhance purity: minimizing the presence of residuals, empty capsids, or contaminants. Extensive analytical expertise will also be critical for purity and safety assessment while demonstrating the absence of potential risks to patient health.

Considering scale

Delivering new therapeutics to market successfully requires scalable manufacturing processes that have been optimized with cost in mind, as higher production prices will limit patient access.

However, building robust processes and analytical methods while working with a relatively new drug modality is challenging. This is compounded by the fact that the production of advanced therapies like gene editing technologies will cost significantly more than conventional biologics such as monoclonal antibodies (mAbs).

By working with contract development and manufacturing organizations (CDMOs) with extensive experience in viral vector manufacturing, drug developers can be assured that processes have been built with consideration to scalability and cost. As a result, critical new therapies can be delivered to a broader patient population faster.

New technologies bring unique challenges

Potentially unfamiliar challenges are likely to arise when working in new areas like gene editing. The regulatory landscape governing these technologies will initially be dynamic and, as the gene editing space matures, requirements will evolve in tandem. Growing evidence from preclinical and clinical trials as well as advances in analytical techniques will act to mold the regulations governing the gene editing space. As a result, developers and manufacturers must demonstrate flexibility while staying abreast of innovations, industry advancements, and evolving regulations.


A Look to the Future

The potential for gene editing to rectify genetic abnormalities in patients’ cells and effectively cure genetic disorders is an attractive prospect that could be within grasp in the not-so-distant future. Realizing this possibility, however, will rely on the effective development and manufacturing of new therapies at scale, likely giving rise to unique challenges. Navigating the difficulties ahead and making gene editing a reality for patients will necessitate manufacturers with proven expertise in areas like viral vector production and analytics.

To find out more about how Andelyn Biosciences can help with your next viral vector project, contact us today.