On the acceleration of gene editing: what’s next?

Tim Farries, PhD

A timely panel debate is coming, and Biopharma Excellence will be privileged to moderate it, says Tim Farries, PhD, Principal Consultant & Senior Director

After decades of talk and expectation, the first generation of medicinal products incorporating genome editing, also known as gene editing, is finally nearing approval. In the meantime, ever more advanced approaches are progressing through clinical development, such that new waves of progress are likely to come thick and fast now.

But where will this take us, what is the promise, and what are the issues still to be ironed out, as experimental therapies take form and gradually become a reality? For example, how fit for purpose is the regulatory environment? Are the risks understood, and how can these be quantified and mitigated?

By its very nature, genome editing is a sensitive area of research, seeking as it does to modify genes with a view to developing targeted treatments for genetic or acquired diseases; and – wherever possible and appropriate – preventing these from developing in the first place.

Technology-wise, we’re seeing particular progress with both ex vivo and, now also, in vivo approaches and techniques. The ex vivo approach takes cells from the individual, modifies them outside of the body and then puts them back into the patient, while in vivo approaches involve treating patients with viral vectors, or other methods that provide the machinery to modify the genomes of the patient’s cells while still in the body.

On the positive side, in vivo genome editing provides a means to treat tissues which, unlike blood cells, cannot readily be extracted and re-administered to the patient after modification – yet with the negative corollary of exposing off-target cells and tissues to the risk of modification (germ-line cells are of particular concern in this regard).

Beyond the lab

The potential of these cutting-edge developments is clearly considerable, but what can we expect; which technologies will prove to be the most reliable; what could still go wrong; and what might set back the field if not planned for now? There is still much to be smoothed out.

There is much expectation around CRISPR-Cas9, for instance, which was adapted from a naturally occurring genome editing system that bacteria use as an immune defense. But what makes for a versatile laboratory tool is not necessarily the most appropriate system available for therapeutic applications.

And of course, the real potential goes beyond the immediate technology. Take the genetic analyses that go with this: the power and the implications of whole genome sequencing (WGS) – a next-generation sequencing application that determines the entire DNA sequence all at once. What could this mean, and what will be expected?

Areas of potential

An area that is especially exciting currently is the ability to edit pluripotent stem cells. These stem cells have the ability to undergo self-renewal, and to give rise to diverse cells of the tissues of the body. There is huge potential here in terms of the therapies that we may be able to create.

In terms of in vivo genome editing, there’s now the potential to go in and repair or edit DNA in vivo rather than ex vivo. The ability to do that directly in vivo would open up a world of new opportunity, though it’s still very early days for this.

The real proof of the value of the technology will be revealed by results in the clinic. By the same token, clinical experience will surely show up safety issues.

With great opportunity, comes great risk

All of this potential, yet to be realized, highlights the factors that sponsors and investors will need to be aware of, particularly linked to identifying and controlling risks.

One of the difficult issues that remains with gene therapy surrounds delivery – i.e. how to ensure the right tissues, with the right efficiency.

The trouble with cells is that they can do bizarre things. Currently genetic technology is being applied in a fairly restricted space. Start mixing that with something as versatile as stem cells to tackle otherwise difficult to treat diseases, such as disorders of the central nervous system, and the potential for the unexpected is even greater.

Such risks need to be managed as well as possible. This matters hugely to investors too.

The key is to draw on smart advice and maximize planning.

Up for debate: it’s time to thrash out the detail

With all of these emerging opportunities and practical considerations in mind, I’ll be chairing the genome editing panel debate entitled Gene Editing Accelerates: The First Generation Nears Approval While New Approaches Progress Through the Clinic at the 2022 Cell & Gene Meeting on the Mesa at 4PM-5PM on Tuesday October 11.

The session is designed to air the emerging opportunities and dig deep into the challenges. We expect it to appeal to everyone from development scientists, CEOs, and Chief Development and Chief Scientific Officers, to anyone else with an interest in genome editing.

It will be a chance to learn about the latest developments in the field; where each respective organization’s current activities fit into the broader picture; potential barriers they may not yet have considered; and where innovators and their backers might benefit from broader connections.

It will be a chance to get a better feel for what’s going on, from those involved at the front line rather than just what’s been published in the literature and guidelines.

Confirmed panelists to date include experts from:

  • Arbor Biotechnologies
  • LogicBio
  • Editas Medicine
  • Intellia Therapeutics

You can find the full agenda here.

I hope you’ll join us for what promises to be a lively and thought-provoking session!

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