Intro 

Delivery of therapeutics to the brain during early development presents a unique opportunity to treat disease prior to the onset of irreversible brain changes, and at a time with increased tolerance to new proteins. However, the blood-placenta-barrier and fetal blood-brain-barrier have posed substantial challenges to perinatal brain drug delivery.  

 

Objectives 

Here we explore the potential of a transferrin receptor (TfR) binding therapeutic platform that we call the “transport vehicle” (TV) to enable delivery of drugs, specifically oligonucleotides, in the neonatal brain.  

Methods 

To assess this, neonatal mice were treated with subcutaneous injections of a malat1 targeted, oligonucleotide-TV conjugates (OTV) at postnatal days 1, 3, 7, 10 and 13 (n=4-8/group). Brain tissue was collected at postnatal days 3, 7 and 14. 

 

Results 

We find that the OTV platform enables delivery of a malat1 targeted ASO, to the brain at early developmental stages. Furthermore, we observe that binding to TfR alters the biodistribution of antibodies and oligonucleotides to the brain.  

 

Conclusions 

These data support the TV platform and OTVs as a potential therapeutic platform for systemic delivery of drugs to the perinatal brain.