TRACER Platform

Novel AAV-based capsids harness the extensive vasculature of the central nervous system.

The Problem

Delivery of medicines into the brain is hampered by the blood-brain barrier.

  • Small molecules cross the BBB, but cannot effectively modulate many targets (considered “undruggable”)1
  • Oligonucleotides require intrathecal injection, creating steep gradients in the CNS2
  • Antibodies can cross into the brain but have a 0.1-0.5% brain to plasma ratio, requiring high doses3
  • Gene Therapy: direct injection (Intra-Parenchymal, Intra-Cerebro Ventricular, Intra-Thecal, Intra-Cisterna Magna) can result in patchy delivery, inadequate brain distribution, low transduction efficiencies, and safety concerns4,5

References: 1) Mitiksh, et. al., Perspect Medicin Chem. 2014; 6: 11–24. 2) Mazur, et. al., JCI Insight. 2019 Oct 17; 4(20): e129240. 3) Tang,, Drug Discovery Today. 2021; 26.8. 4) Bey, Mol Ther Meth Clin Dev, 2020. 5) Zincarelli et al., 2007.

The Solution

Voyager’s TRACER™ (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) capsid discovery platform is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier and enhanced central nervous system (CNS) tropism in multiple species, including non-human primates (NHPs).

The TRACER Difference

IV delivery:

minimally invasive

Multi-species validation:

multiple species of non-human primates and rodents

Receptor identified:

verified existence of human homolog; increases confidence in human translation

CNS penetration:

>100-fold improved delivery over AAV9 (ASGCT 2022)

CNS transduction:

up to 40% cells transduced in multiple brain regions at relatively low dose of 4e12 vg/kg in cynomolgus macaques (In Vivo Gene Editing and Gene Therapy Summit, 2023)

Liver de-targeting:

up to 30X improved liver de-targeting versus AAV9 in mice (ASGCT 2023)

Customizable cell tropisms:

can target neurons and/or glial cells

Relatively low doses:

50% cells transduced in multiple brain regions at 2E12 vg/kg in marmosets (ASGCT 2023)