Using Targeted Locus Amplification to Analyze Genetically Modified Cells

Solvias’ Targeted Locus Amplification (TLA) platform is a tool for analyzing the genome of cells that have been genetically modified outside the body by viral vectors. At the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, Daniel Galbraith, PhD, the chief scientific officer of Solvias, presented on the use of TLA for analysis of lentivirus integration and mechanisms.

At the conference, CGTLive® asked Galbraith about the key points from his presentation and their implications. Galbraith also discussed potential future plans for the use of the TLA platform, highlighting a potential ability to assess how genetically modified cells have changed after reinfusion back into the patient.

CGTLive: Can you give some background about what you presented?

Daniel Galbraith, PhD: We presented on a technology called TLA. TLA is a way of analyzing a genome that you've inserted a viral vector into—so if you want to understand how many copies of the vector are in that genome, has the insertion caused any problems with the genome? Has it changed anything within the genome? It's really important to understand that because if you've inserted your vector into an oncogene, or something like that—if you've upset an oncogene, then that could have real severe effects on the patient if you're then using that cell to treat the patient.

Can you give an overview of the key points of your presentation?

We described really how the how the assay works—what's needed for the assay, how long it takes, and how much it costs it to actually do, which is obviously important. What we also describe is the types of changes that we can see, how sensitive the method is to actually see those changes, and what we also look at is how these changes can evolve over a period of time. You can imagine, if you've treated a population of cells, those cells are growing and changing, and these insertions can also cause different changes to happen, and so that population will evolve over time. We can look at that and look at those changes. So if you're culturing cells over 2 or 3 weeks, we can look at these changes and how they are affected over the weeks.

How would you summarize the big picture implications that you would want doctors and the broader healthcare community to take away from this?

There are risks associated with gene therapy. One of the big risks is you don't want to do any damage to the patient. Obviously, these patients are ill and you want to help them as much as you can, so making sure that your treatment is not going to cause any damage is the important thing. This technology, TLA, will give us a good indication that it's not actually going to cause any cancer effects from the treatment that you're going to give. It gives you a level of safety that you're actually not going to do any harm. That's really the takeaway message for using this type of technology.

Are there any future plans for this technology that you can discuss?

At the moment, what we do is we actually look at the cells before they're administered to the patient. We've usually taken the cells from the patient, modified them with the virus, and then they go back into the patient, and we do the test at that stage. But then the question is, once they're back in the patient, what happens then? These cells can last for quite a while when they're put back into the patient, so we want to ask that question after they've been administered: can we then look at them and see how these changes have been? So I think in the future, we'll do the pretreatment, and then we'll do the posttreatment—and so harvest back from the patients and actually look at the cells and see how they've evolved and changed, and then it gives us a better indication over a longer period if these cells are safe to use.

Is there anything else you want to share?

I think one other thing to bear in mind is that these technologies are very early. Don't be surprised that they will not be on the market for very long. I think people will evolve them over a period of time and I think the technologies, as I was describing, will be useful in actually understanding how these technologies work. I think there's a long way to go with these new healthcare treatments, and this is probably how it's going to be in the immediate future.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.