BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model.

Hematopoietic stem cell (HSC) gene therapy has curative potential; however, its use is limited by the morbidity and mortality associated with current chemotherapy-based conditioning. Targeted conditioning using antibody-drug conjugates (ADC) holds promise for reduced toxicity in HSC gene therapy. Here we test the ability of an antibody-drug conjugate targeting CD117 (CD117-ADC) to enable engraftment in a non-human primate lentiviral gene therapy model of hemoglobinopathies.

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Rats.

Buprenorphine (Bup) is an opioid analgesic that is commonly used in laboratory rodents to provide postoperative analgesia. However, dosing every 4 to 6 h is necessary to maintain an analgesic plasma concentration of the drug. A long lasting, highly concentrated veterinary formulation of Bup (LHC-Bup) has been used to provide prolonged analgesia in cats and nonhuman primates.

Effects of Compressed Paper Bedding on Mouse Breeding Performance and Recognition of Animal Health Concerns.

The combination of bedding substrate and nesting material within the microenvironment of mice is an important consideration for animal care programs in regard to optimizing animal wellbeing. We used 3 general or breeding mouse colonies in our institution to evaluate the effects of bedding substrate on nest building, breeding performance, and recognition of animal health concerns. A scoring system was developed to assess the incorporation of bedding into the nest cup base and walls (nest base incorporation, NBI) in a controlled study with mice bedded on either compressed paper (CP) or corncob (CC) bedding.

Effects of exercise in a relapsing-remitting model of experimental autoimmune encephalomyelitis.

Previous research has examined the effects of exercise in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. However, all previous studies have utilized a chronic model of EAE, with exercise delivered prior to or immediately after induction of EAE. To our knowledge, no study has examined the effects of exercise delivered during a remission period after initial disease onset in a relapsing-remitting model of EAE (RR-EAE).