Automated Stem Cell Editing Could Expand Gene Therapy Manufacturing, ASTCT Expert Says

An automated system produced gene-edited hematopoietic stem and progenitor cells with 20% to 25% targeted gene integration, matching laboratory processing, and maintained a similar proportion of edited cells after transplantation into mice. Matthew Porteus, MD, PhD, of Stanford Medicine, presented the preclinical findings during the 2026 American Society for Transplantation and Cellular Therapy Gene Therapy Summit in Boston, describing a potential route toward manufacturing cellular medicines at greater scale.¹

“We were able to get 20% to 25% integration, which is the same frequency of integration we get in the laboratory,” Porteus said.¹ The results do not demonstrate treatment effectiveness in patients, but address a central obstacle to expanding access: producing individually manufactured cell products consistently without relying entirely on labor-intensive processes.

Automating Gene Editing Without Losing Function

Porteus described collaboration with Cellares to transfer a hematopoietic stem cell editing workflow into its enclosed Cell Shuttle manufacturing system. The platform integrates cell preparation, CRISPR-Cas9 editing, and harvest. In this experiment, investigators inserted an antibody-encoding transgene at the CCR5 locus in CD34-positive cells. A preprint published October 30, 2026, describes clinical-scale production and gene knock-in efficiencies reaching 24.7%. These results have not yet undergone peer review.²

Engraftment presented another critical test. After automated cell products were transplanted into mice, gene-modified cells remained detectable across blood lineages, with approximately 20% to 23% targeted integration among engrafted cells. This is an editing-related measurement, not the percentage of all transplanted cells that engrafted.

“We got 20 to 23 percent stable engraftment in the mouse,” Porteus said.¹ The experimental platform can accommodate up to 16 manufacturing cartridges in parallel, although this capacity does not establish routine clinical production or lower patient prices.²

Porteus argued that scaling cell therapy may ultimately resemble industrial manufacturing: “automobiles are also complicated to make, and the solution was not to make automobiles in everyone's backyard.”¹ He emphasized that automated production could reduce repeated manual processing while maintaining product quality, an especially relevant issue for individualized gene-edited therapies.

Choosing Between Cellular and Gene-Based Medicines

The presentation challenged a familiar division between treatments performed outside the body and those delivered directly into it.

“What I'd like to convey is that I think we shouldn't be thinking about ex vivo versus in vivo, but we should be thinking about what the drug is,” Porteus explained.¹

In cellular medicines, the administered product is a population of cells that may expand and migrate after infusion. Gene-based medicines instead deliver genetic material through vectors or particles, whose biodistribution and immune effects depend on the delivery platform. Ex vivo processing permits characterization of edited cells before infusion; in vivo editing presents different challenges for measuring where and how frequently genetic changes occur.

Porteus also cautioned that “in vivo does not necessarily mean cheaper.”¹ Lipid nanoparticles can simplify some aspects of individualized manufacturing, but manufacturing cost, dose requirements, immune responses, and safety monitoring remain important considerations.

One approaching regulatory test is lonvoguran ziclumeran (Intellia Therapeutics), an investigational lipid nanoparticle-delivered CRISPR therapy for hereditary angioedema. In a phase 3 trial (NCT06634420) involving 80 participants, the treatment reduced the monthly attack rate by 87% relative to placebo during the efficacy evaluation period.³ Its FDA application received priority review and has a target decision date of March 10, 2027; however, approval is not guaranteed.⁴

Engineered Stem Cells as Long-Acting Drug Producers

Porteus described research extending beyond correcting individual disease-causing mutations. Engineered hematopoietic stem cells could potentially generate B cells that secrete therapeutic monoclonal antibodies for extended periods, replacing repeated drug administration with sustained biological production.

“We think there's a possibility that this continuous steady state delivery of a biologic could have safety and efficacy improvements,” he said.¹

In preclinical work, investigators engineered stem cells to produce antibodies targeting PCSK9 or tumor necrosis factor α. In mice, antibody concentrations persisted for about 16 weeks, but the experiments did not establish clinical efficacy, safety, or lifelong dosing in humans.⁵

The concept could alter how pharmacists think about exposure and dose adjustment. Unlike conventional biologics that can be withheld or modified, durable antibody production from an engrafted cell population may prove harder to reverse. The appropriate clinical controls remain questions for future development.

Porteus described the broader ambition as “developing gene editing as something that would become a platform for all of medicine, just like biologics have become.”¹

Gentler Conditioning Remains Essential

Even if cell manufacturing becomes more efficient, patients may still need toxic conditioning to create space for modified stem cells. Porteus said “the goal is develop an outpatient fertility-preserving conditioning regimen that is as easy on the patient as possible.”¹

He highlighted briquilimab (Jasper Therapeutics), an antibody targeting CD117, as an alternative to busulfan or irradiation in some transplantation settings. In a published phase 1b Fanconi anemia study (NCT04784052), 3 patients achieved donor engraftment using briquilimab-based conditioning without busulfan or irradiation. The regimen still included cyclophosphamide, fludarabine, rabbit antithymocyte globulin, and rituximab; it was not chemotherapy-free.⁶

For pharmacists involved in transplant and cellular therapy, next-generation approaches raise practical questions about conditioning safety, immune reactions to delivery platforms, individualized product release and long-term drug exposure. Those responsibilities will remain even if automation accelerates manufacturing.

The significance of the reported editing results lies in showing that a complex laboratory workflow can move toward standardized production without an obvious loss of gene-modified cell function in preclinical testing—not in demonstrating a finished, broadly accessible treatment.

REFERENCES

1. Porteus MH. Beyond ex vivo: preparing for the next generation of genetic medicines. Presented at: ASTCT Gene Therapy Summit; November 5, 2026; Boston, MA.

2. Castelli JM, Afangbedji N, Luna SE, et al. End-to-end, fully automated manufacturing of hematopoietic stem and progenitor cell therapy via CCR5-targeted integration. bioRxiv. Preprint posted October 30, 2026. doi:10.64898/2026.10.28.758978

3. Cohn DM, Gurugama P, Longhurst HJ, et al. Lonvoguran Ziclumeran - In Vivo CRISPR Gene Editing in Hereditary Angioedema. N Engl J Med. 2026;395(15):1471-1482. doi:10.1056/NEJMoa2600931

4. Intellia Therapeutics announces FDA acceptance of biologics license application with priority review for lonvoguran ziclumeran (lonvo-z) for hereditary angioedema (HAE). News release. Intellia Therapeutics. September 8, 2026. Accessed November 5, 2026. https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-fda-acceptance-biologics-license

5. Porteus M, Luna S, Feist W, et al. Engineered hematopoietic stem cells give rise to therapeutic antibody secreting B cells. Preprint. Res Sq. 2026;rs.3.rs-9269825. Published 2026 Apr 6. doi:10.21203/rs.3.rs-9269825/v1

6. Agarwal R, Bertaina A, Soco C, et al. Irradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial. Nat Med. 2025;31(9):3183-3190. doi:10.1038/s41591-025-03817-1