Quick Q&A with ViaCyte CEO on CRISPR-stem cell work

VC-01 post-implant final
ViaCyte's VC-01 post-implant

We heard this week about the encouraging news of a new CRISPR-stem cell collaboration between stem cell biotech ViaCyte and CRISPR Therapeutics. The goal of the team is to make genetically engineered pancreatic derivatives from stem cells that would have a unique immune stealthiness. If such an approach was successful, patients would not need to take immunosuppressive drugs. I followed up with five questions for ViaCyte. Their CEO Paul Laikind sent along some answers that provide new, deeper insights. You can see a cool image of staining of one of ViaCyte’s pancreatic devices at right.

VC-01 post-implant final
ViaCyte’s VC-01 post-implant

What is the advantage of a gene editing-based strategy for immune evasion over giving patients immunosuppressive drugs?

ViaCyte: The advantage of an islet cell replacement therapy that has been gene-edited for immune evasion is simply that patients would not need to take immunosuppressive drugs, which can have side effects.  Our main mission is to improve the lives of patients with  insulin-requiring diabetes by delivering transformative new therapeutic options. The work we are doing on PEC-Direct, PEC-Encap, and now an immune-evasive approach, known as PEC-QT, are all a part of that mission.

What timeline is envisioned for getting to an IND for the new gene-edited product?

ViaCyte: The agreement between CRISPR and ViaCyte to develop an immune-evasive stem cell line is a first step on the path to an allogeneic stem cell-derived product.  These are early days for this collaboration, and as we advance the program, we can provide additional milestone and timeline updates.

I see four trial listings for ViaCyte on Clinicaltrials.gov. How are things going with VC-01 and the current VC-02 trials? Does VC-01 have a future?

ViaCyte: Yes, indeed the PEC-Encap (also known as VC-01) product candidate has a bright future!  We remain enthusiastic regarding the prospects of PEC-Encap, and are actively working on it.  In June, two-year data from ViaCyte’s STEP ONE clinical trial were presented at ADA 2018.  Although consistent and robust engraftment has been limited in this study to date, results showed that when engraftment does occur, viable mature insulin-expressing endocrine islet cells can be formed.  In some cases, insulin-expressing cells have persisted for up to two years after implantation, the longest time point investigated in the study.

Building on insights gained during the STEP ONE study, ViaCyte is working with W.L. Gore & Associates, one of the world’s top materials science companies with expertise in medical device development and drug delivery technologies, to modify the Encaptra Cell Delivery System and improve the potential for long-term engraftment.  This work has yielded positive results in non-clinical models that, based on clinical experience, have been selected to reflect the response in patients.  If the progress continues as expected, we plan to resume STEP ONE trial enrollment in 2019.

As for PEC-Direct (also known as VC-02), the Phase 1/2 clinical evaluation of that product candidate is also continuing.  We are now evaluating patients in the second cohort of the trial.  As you know, PEC-Direct has the potential to help the patients with type 1 diabetes with the greatest need.

We view PEC-Direct, PEC-Encap, and PEC-QT as a multigenerational program.  Besides in some cases targeting different patient populations, this multigenerational strategy provides for multiple paths to our ultimate goal of providing a functional cure for patients with type 1 diabetes and new treatment options for insulin-requiring type 2 patients.

Does ViaCyte have any plans for work beyond diabetes?

ViaCyte: Our technology is applicable in a number of different disease areas, and we will evaluate the opportunities when the time is right.

How is what you are doing different than that of the company Universal Cells that was acquired by Astellas?

ViaCyte: With CRISPR Therapeutics we will be using CRISPR/Cas9-based gene editing technology, whereas Universal Cells uses recombinant adeno-associated virus technology to modify the stem cell DNA.  Many candidate targets exist beyond what Universal Cells has disclosed.

Our real power comes in our expertise to scale and differentiate stem cells into pancreatic cells suitable for cell replacement.  ViaCyte was the first to describe directed differentiation of human pluripotent stem cells into pancreatic cells, and the first to demonstrate the differentiation of stem cell-derived pancreatic progenitor cells into glucose-responsive insulin-producing cells, both in vivo and in vitro.  ViaCyte’s patent portfolio includes more than 700 issued patents worldwide, and protection in the space extends for the next two decades or more.

4 Comments


    • Was asking myself the same question. Classical immunosuppressive receptors, such as PD-1 and CTLA-4 etc could be activated on immune cells (CTLs, NK cells) by cloning their ligands (PD-L1/2 and B80/86 or fragments thereof) as surface expressed proteins onto the beta cells. Basically copying how tumors evade the immune system (and they´re very good at it). But I wouldn´t want to be a regulator when this application arrives.


  1. Check out one method developed by Universal Cells: http://www.universalcells.com/
    It involves knocking out Beta 2 microglobulin, which is necessary for MHC1 (HLA1) to be expressed at the cell surface. To avoid having HLA1-negative cells being attacked by natural killer (NK) cells, they add a different HLA – single chain HLA-E. They also get rid of HLA2 by knocking out a gene called RFXANK. Instead of CRISPR, they use an AAV method. But the knockouts could be achieved using CRISPR technology.

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