Systemic Toxicity of Recombinant Adeno-Associated Virus Gene Therapy Vectors.

Recombinant adeno-associated virus (rAAV) vectors have emerged as a promising tool for gene therapy. However, the systemic administration of rAAV vectors is not without risks, particularly for dose levels >1 × 10 viral genome per kilogram of body weight (vg/kg). rAAV-associated toxicities can variably manifest either acutely or in a delayed manner.

Endovascular Conversion of a Failed Nellix AAA-Repair by a Custom-Made Branched Device.

Purpose: This technical note presents a case of a patient with a failed Nellix device (Endologix, Irvine, Calif) who was not deemed fit for open conversion. Our planned approach for repair involved an endovascular procedure utilizing a custom-made branched device.

Technique: An endovascular repair was performed via a custom-made four outer branched device in conjunction with a custom-made bifurcated graft featuring inverted limbs (Cook Inc.

Scientific and Regulatory Policy Committee Technical Review: Biology and Pathology of Ganglia in Animal Species Used for Nonclinical Safety Testing.

Dorsal root ganglia (DRG), trigeminal ganglia (TG), other sensory ganglia, and autonomic ganglia may be injured by some test article classes, including anti-neoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, nerve growth factor inhibitors, and aminoglycoside antibiotics. This article reviews ganglion anatomy, cytology, and pathology (emphasizing sensory ganglia) among common nonclinical species used in assessing product safety for such test articles (TAs). Principal histopathologic findings associated with sensory ganglion injury include neuron degeneration, necrosis, and/or loss; increased satellite glial cell and/or Schwann cell numbers; and leukocyte infiltration and/or inflammation.

CBFA2T3-GLIS2-dependent pediatric acute megakaryoblastic leukemia is driven by GLIS2 and sensitive to navitoclax.

Pediatric acute megakaryoblastic leukemia (AMKL) is an aggressive blood cancer associated with poor therapeutic response and high mortality. Here we describe the development of CBFA2T3-GLIS2-driven mouse models of AMKL that recapitulate the phenotypic and transcriptional signatures of the human disease. We show that an activating Ras mutation that occurs in human AMKL increases the penetrance and decreases the latency of CBF2AT3-GLIS2-driven AMKL.