Abstract Details

Title Premature Labor in the Domestic Sow in Response to in utero Delivery of AAV9 to Fetal Piglets

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S42 - Neuromuscular Disorders (3:52 PM-4:03 PM)

Poster/Presentation
Number 003

Background For some gene therapy applications, there is increased interest to deliver gene cargo in utero to maximize effectiveness.

Objective

To deliver adeno-associated virus, serotype 9 (AAV9) constructs safely to fetal piglets in anticipation of clinical applications where delivery of gene cargos in utero may maximize therapeutic efficacy.

Design/Methods We performed a series of ultrasound-guided in utero injections in the domestic piglet under conditions that mimic the delivery of AAV9-mediated gene therapy to human fetuses. There were five rounds of injections that occurred in sows at gestational ages ranging from GA77 to GA 110. During each round, a single pregnant sow was anesthetized, viable piglets were visualized by ultrasound and injections occurred in up to three piglets. In two rounds, AAV9-shSMN was injected that delivers a short hairpin RNA against the piglet Smn gene. In another two rounds, AAV9-GFP was injected that delivered the gene encoding green fluorescent protein, and in one round, a sham injection of phosphate buffered saline was delivered.

Results The procedures occurred without complication and injection of material was directly visualized via ultrasound. In all rounds involving AAV9-shSMN and AAV9-GFP, spontaneous abortion of all fetuses occurred between two and seven days after procedure. No viable piglets were observed. In the sham injected round, the sow carried all piglets to farrow.

Conclusions Delivery of AAV9 in utero to piglets is associated with premature labor of non-viable piglets. The in utero delivery paradigm applied here provides insight into the feasibility of early gene delivery in the domestic sow and suggests caution in the application of in utero AAV9 delivery in humans.

Authors/Disclosures
Christopher Wier PRESENTER	No disclosure on file
	No disclosure on file
Mehmet E. Yalvac, PhD (The Ohio State Univ. Dept. of Neurology)	Dr. Yalvac has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stephen J. Kolb, MD, PhD (The Ohio State University)	Dr. Kolb has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AveXis. Dr. Kolb has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CureSMA. The institution of Dr. Kolb has received research support from NIH. The institution of Dr. Kolb has received research support from AveXis. The institution of Dr. Kolb has received research support from NIH.

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