Generation Bio Overcomes Gene Therapy Limits with ceDNA in Hemophilia A


In a press release from early January 2021, genetic medicines company Generation Bio Co. (“Generation Bio”) announced data from a variety of studies. In one, the company shared that it used its novel cell-targeted lipid nanoparticle (ctLNP) technology to deliver closed-ended DNA (ceDNA) to mice models of hemophilia A. Through this, Generation Bio achieved not only dose tolerability, but desired factor VIII expression levels. In other ceDNA-related studies, researchers were able to use ceDNA and ctLNP to deliver doses to both men and non-human primates. Additionally, it shows the translation of novel, liver-directed ctLNPs.

ceDNA and ctLNP

After using ceDNA and ctLNP, Generation Bio did see some achievements in their non-viral gene therapy program. Some of these milestones include:

  • One dose of intravenously-administered ceDNA was expressed for months in the livers of mice with hemophilia A.
  • ceDNA-ctLNP was relatively well-tolerated in doses of 0.5mg/kg, 1.0mg/kg, and 2.0mg/kg.
  • Following one 2.0mg/kg dose of ceDNA, mice with hemophilia A saw a 23% increase in factor VIII expression within 10 days. The increase was 16% for those taking a 1.0mg/kg dose, and 9% for those taking a 0.5mg/kg dose.
  • Because ceDNA-ctLNP does not create antibodies, as some other gene therapies do, ceDNA can be re-dosed. For example, after re-dosing mice after 5 weeks, researchers saw an increase in factor IX protein.
  • Researchers were able to track translation of expression between mice and non-human primates through weight-adjusted doses of ceDNA-ctLNP. In one study, researchers saw an increase of ~1% in both non-human primates and mice within 5 and 7 days, respectively. In a secondary study, researchers saw a ~3% increase in mice at day 5, which translated pretty similarly in non-human primates.
  • ceDNA and ctLNP were relatively safe and well-tolerated. No adverse reactions occurred. Both the liver and spleen were protected from damage.

Hemophilia A

Also known as factor VIII deficiency or classic hemophilia, hemophilia A is an inherited bleeding disorder. Patients with hemophilia A lack enough factor VIII, a type of clotting protein. Thus, the blood fails to clot properly, causing excessive bleeding. Men are more likely to develop this disease than women. Symptoms include:

  • Frequent and easy bruising and bleeding
  • Digestive and urinary tract bleeding, causing bloody stool or urine
  • Excessive nose bleeds
  • Bleeding after cuts, trauma, dental work, or surgery
  • Joint pain and swelling
  • Excessive menstruation or bleeding after childbirth (for females)
  • Irritability

Learn more about hemophilia A here.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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