Blood cells taken from mice with Hemophilia B that were induced to become stem cells, edited using CRISPR technology, grown into hepatocyte-like cells and transplanted back into the patients restored the ability to form blood clots for a year.

People suffering from the inherited blood disorder hemophilia B either lack or have a faulty F9 gene, which codes for clotting factor IX (FIX). As a result, no or very little FIX is produced and even the smallest cuts can lead to life-threatening bleeding.

The current treatment for hemophilia B patients consists of frequent injections of clotting factors – in some cases several times per week – an expensive and time-consuming proposition that can negative impact patient adherence. Researchers at the Salk Institute may have a more attractive alternative.

After discovering that injecting mouse models of hemophilia B with messenger RNA encoding for the FIX gene only restored the ability to produce clotting factors for less than a week, the scientists decided to tackle the problem at the source. They sought a way to transplant liver cells into hemophilic mice, but without needing entire organs, for which there is a constant supply issue.

Their solution – develop synthetic livers starting with blood cells from the hemophilia B mouse models. The blood cells were programmed into induced pluripotent stem cells, edited using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, coerced into forming liver precursor cells (hepatocyte-like cells, HLCs) and then injected into the mice. 

The results were promising. Clotting function was restored at a level “at least 10-fold higher than the levels that would be needed for a significant improvement in treating the disease” and lasted for at least one year. This approach, if it can be translated to humans, also has the advantage of avoiding immune responses since the each patient’s own cells are used.

In a different approach, Spark Therapeutics is developing a gene therapy (SPK-9001) that delivers a functional copy of the gene rather than involving editing of the gene followed by infusions of cells. Nine out of 10 patients in a phase 1/2 trial experienced no bleeding episodes one year after gene therapy treatment.