Genetic Engineering in the Press by GEG

Hereditary angioedema (HAE) is a rare genetic disorder characterized by severe inflammatory attacks accompanied by swelling of various organs and tissues. Plasma kallikrein is a protein known to drive multiple inflammatory pathways, including the production of the inflammatory mediator bradykinin, which is overproduced in HAE. Researchers have therefore developed the NTLA-2002 treatment, which is designed to eliminate the target gene kallikrein B1 in hepatocytes. It is administered intravenously as a single dose of Cas9 mRNA and gRNA via lipid nanoparticles. Preclinical studies have demonstrated a sustained and therapeutically relevant reduction in plasma kallikrein activity after a single dose in non-human primates, and the candidate is currently being evaluated in a Phase 1/2 combination clinical trial to assess its safety, tolerability, pharmacokinetics and pharmacodynamics. Clinical data from the Phase 1 dose-escalation portion of this trial showed that a single dose of NTLA-2002 produced robust, dose-dependent and durable reductions in total plasma kallikrein levels, and no serious adverse events were observed. In addition, a reduction in the number of angioedema attacks per month was observed at all dose levels (25 mg, 50 mg or 75 mg).

A permanent cure for HIV infection remains elusive due to the virus's ability to hide away in latent reservoirs. But now, in new research published in print May 3 in the journal Molecular Therapy, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh show that they can excise HIV DNA from the genomes of living animals to eliminate further infection. They are the first to perform the feat in three different animal models, including a “humanized” model in which mice were transplanted with human immune cells and infected with the virus.