Unmet Need:
Gene delivery to the central nervous system (CNS) has potential as a means for treating numerous debilitating neurological diseases. Viral gene delivery, though relatively efficient, has been limited by immunogenicity, low packaging capacity and difficulties in manufacture and scale-up. Non-viral gene vectors offer an attractive alternate strategy for gene delivery, but diffuse and homogeneous transgene delivery in the CNS constitutes an important challenge to effective gene therapy and the anisotropic and electrostatically charged extracellular matrix (ECM) found between brain cells creates a brain tissue barrier which, regardless of administration method, hampers widespread distribution of nanoparticles in the brain.
Technical Overview:
Encouragingly, Johns Hopkins researchers generated cationic polymer based brain penetrating nanoparticles (BPNs) by blending polyethyleneimine (PEI) with a copolymer at specific ratios. Brain tissue treated with BNPs carrying a transgene showed widespread distribution and higher transfection efficiency of the transgene compared to conventional controls in brain tissues. They have shown that sub-100 nm nanoparticles exceptionally well coated with hydrophilic and neutrally charged polyethylene glycol (PEG) rapidly diffuse in the brain ECM allowing the widespread distribution of therapeutics. Advantages include:
Stage of Development:
Preclinical
Publication(s):
1. Mastorakos et al. Highly PEGylated DNA Nanoparticles provide Uniform and Widespread Gene Transfer in the Brain. Adv. Healthc. Mater. 2015 May; 4(7): 1023-33
2. US Patent 9,937,270
3. AU Patent 2015259362
4. WO2015175539A1
5. Small. 2019 Dec;15(49):e1903460
6. J Control Release. 2019 Jun 10;303:1-11
