Transcutaneous ultrasound-mediated gene delivery into canine livers achieves therapeutic levels of factor VIII expression
Year: 2022
Type: article
Abstract: A safe, effective, and inclusive gene therapy will significantly benefit a large population of patients with hemophilia. We used a minimally invasive transcutaneous ultrasound-mediated gene delivery (UMGD) strategy combined with microbubbles (MBs) to enhance gene transfer into 4 canine livers. A mixture of high-expressing, liver-specific human factor VIII (hFVIII) plasmid and MBs was injected into the hepatic vein via balloon catheter under fluoroscopy guidance with simultaneous transcutaneous UMGD treatment targeting a specific liver lobe. Therapeutic levels of hFVIII expression were achieved in all 4 dogs, and hFVIII levels were maintained at a detectable level in 3 dogs throughout the 60-day experimental period. Plasmid copy numbers correlated with hFVIII antigen levels, and plasmid-derived messenger RNA (mRNA) was detected in treated livers. Liver transaminase levels and histology analysis indicated minimal liver damage and a rapid recovery after treatment. These results indicate that liver-targeted transcutaneous UMGD is promising as a clinically feasible therapy for hemophilia A and other diseases.
Source: Blood Advances
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Awards: Immune Response for Hemophilia After Replacement Therapy, Ultrasound-mediated gene delivery to achieve therapeutic correction of hemophilia A, Nonviral Gene Medicine for Hemophilia A, Development of clinically feasible Ultrasound-mediated gene therapy for hemophilia, Cancer Center Support Grant
OpenAlex ID: W4223922735