Genomic editing of stable universal pluripotent stem cells for allogeneic cell biotherapies


Annelise BENNACEUR – UMS 45
Inserm – Paris Saclay University

Key words

Universal iPSC
GMP Bioproduction
Immunity assay
Allogenic Cell Therapies (CAR Macrophage, Neural cells)

Key figures
  • Budget : 4 M€
  • Duration : 4 years (2023 – 2027)

The generation of human induced pluripotent stem cells (iPSCs) from adult cells offers a unique opportunity to obtain an unlimited supply of a broad spectrum of specialized cells, for innovative cell therapy strategies in the treatment of cancers, treatment degenerative diseases and as an alternative to organ transplants.

Producing an immuno-compatible or hypoimmunogenic iPSC cell population is an important challenge for promoting allogeneic cell therapies accessible to a large number of patients. iPS cells are particularly suitable for genome editing technology, which makes the development of “universal-donor” iPS lines a possible goal. The main advantage of an iPSC donor line derived from a single genetic background is the ease of preclinical testing, reducing expense and time, compared to the characterization of cell products derived from multiple donors and various iPS cell lines.

The project aims to develop optimal mRNA delivery methods to generate iPSC cells at reduced and controlled costs, preserving genetic integrity and reducing tumor risk. New strategic approaches will be developed to prevent allo-immunogenicity and “universal” iPSC candidates will be evaluated for their differentiation potential specifically in two lineages of clinical interest: the macrophages and neuronal cells. Two pathological models will be studied.

  • Functional study of armed macrophages derived from human iPSC for the treatment of lung cancer
  • Study of the survival and function of iPSC-derived neuron grafts for the treatment of Huntington’s disease (NH primate model).

IPS-France project’s partners bring strong complementary skills in bioengineering of iPSC cells, mRNA delivery and gene editing for the production in CiTHERA platform of a new generation of hypo-immunogenic iPSC in pharmaceutical grade suitable for the manufacture of “off-the-shelf” therapeutic products for future clinical programs.

Coordinating partner : Annelise BENNACEUR – UMS 45
Inserm – Paris Saclay University
Ali TURHAN – UMRS 1310
Inserm – Paris Saclay University
Models of Malignant and Therapeutic Stem Cells (ONCOSTEM)
Inserm – Paris Saclay University
Models of Malignant and Therapeutic Stem Cells (ONCOSTEM)
Chantal PICHON – US55 ART-ARNm
Orléans University
Anselme PERRIER – UMRS 9199
CEA – CNRS – Paris Saclay University
Neurodegenerative Diseases Laboratory