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Transplanting FVIII/ET3-Secreting Cells in Fetal Sheep Increases FVIII Levels Long-Term Without Inducing Immunity or Toxicity

ABSTRACT: Transplanting FVIII/ET3-Secreting Cells in Fetal Sheep Increases FVIII Levels Long-Term Without Inducing Immunity or Toxicity

PROVIDER: PRJNA957430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24219044_1.fastq.gz	Fastqsanger.gz
	SRR24219044_2.fastq.gz	Fastqsanger.gz
	SRR24219045_1.fastq.gz	Fastqsanger.gz
	SRR24219045_2.fastq.gz	Fastqsanger.gz
	SRR24219046_1.fastq.gz	Fastqsanger.gz

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Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity.

Project description:Hemophilia A is the most common X-linked bleeding disorder affecting more than half-a-million individuals worldwide. Persons with severe hemophilia A have coagulation FVIII levels <1% and experience spontaneous debilitating and life-threatening bleeds. Advances in hemophilia A therapeutics have significantly improved health outcomes, but development of FVIII inhibitory antibodies and breakthrough bleeds during therapy significantly increase patient morbidity and mortality. Here we use sheep fetuses at the human equivalent of 16-18 gestational weeks, and we show that prenatal transplantation of human placental cells (107-108/kg) bioengineered to produce an optimized FVIII protein, results in considerable elevation in plasma FVIII levels that persists for >3 years post-treatment. Cells engraft in major organs, and none of the recipients mount immune responses to either the cells or the FVIII they produce. Thus, these studies attest to the feasibility, immunologic advantage, and safety of treating hemophilia A prior to birth.

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Transplanting FVIII/ET3-Secreting Cells in Fetal Sheep Increases FVIII Levels Long-Term Without Inducing Immunity or Toxicity

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