Literature DB >> 27642512

Enhancing Intracranial Delivery of Clinically Relevant Non-viral Gene Vectors.

Sneha Berry1, Panagiotis Mastorakos2, Clark Zhang3, Eric Song1, Himat Patel4, Jung Soo Suk2, Justin Hanes5.   

Abstract

Gene therapy is a promising strategy for the management of various pan class="Disease">neurological disorders that do not respond adequately to conventional therapeutics. The development of gene vectors with favorable safety profiles that can achieve uniform distribution and high-level transgene expression in the brain remains challenging. The rod-shaped, non-viral gene delivery platform based on poly-L-lysine (PLL) conjugated to a single segment of polyethylene glycol (PEG) has shown safe transfection in human nares and mouse brains in vivo. However, we have previously demonstrated that a denser PEG coating is required for rapid diffusion of nanoparticles in the brain extracellular space. Here, we engineered a densely PEGylated version of this platform based on PLL polymers conjugated to branched PEG via alkyne-azide cycloaddition. We found that the newly developed gene vectors rapidly diffused in the brain parenchyma, providing significantly improved vector distribution and overall transgene expression in vivo compared to the previously developed platform. These brain-penetrating DNA nanoparticles exhibited enhanced cellular uptake presumably due to their ellipsoidal morphology. By simultaneously improving delivery to target cells and subsequent transfection, our densely PEGylated PLL DNA nanoparticles can provide widespread, high levels of transgene expression, essential for effective targeting of highly disseminated brain diseases.

Entities:  

Keywords:  Gene therapy; brain extracellular matrix; convection-enhanced delivery; non-viral gene vectors; poly-L-lysine; polyethylene glycol

Year:  2016        PMID: 27642512      PMCID: PMC5019568          DOI: 10.1039/C6RA01546H

Source DB:  PubMed          Journal:  RSC Adv        ISSN: 2046-2069            Impact factor:   3.361


  54 in total

1.  Toll/interleukin-1 receptor domain-containing adapter inducing interferon-β mediates microglial phagocytosis of degenerating axons.

Authors:  Suneil Hosmane; Million Adane Tegenge; Labchan Rajbhandari; Prech Uapinyoying; Nishant Ganesh Kumar; Nitish Thakor; Arun Venkatesan
Journal:  J Neurosci       Date:  2012-05-30       Impact factor: 6.167

2.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells.

Authors:  B Devika Chithrani; Arezou A Ghazani; Warren C W Chan
Journal:  Nano Lett       Date:  2006-04       Impact factor: 11.189

Review 3.  Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers.

Authors:  Julie A Champion; Yogesh K Katare; Samir Mitragotri
Journal:  J Control Release       Date:  2007-04-11       Impact factor: 9.776

4.  The receptor-mediated endocytosis of nonspherical particles.

Authors:  P Decuzzi; M Ferrari
Journal:  Biophys J       Date:  2008-01-30       Impact factor: 4.033

Review 5.  Gene-based therapies in Parkinson's disease.

Authors:  Patricia J Allen; Andrew Feigin
Journal:  Neurotherapeutics       Date:  2014-01       Impact factor: 7.620

6.  Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier.

Authors:  Jung Soo Suk; Anthony J Kim; Kanika Trehan; Craig S Schneider; Liudmila Cebotaru; Owen M Woodward; Nicholas J Boylan; Michael P Boyle; Samuel K Lai; William B Guggino; Justin Hanes
Journal:  J Control Release       Date:  2014-01-14       Impact factor: 9.776

7.  A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity.

Authors:  D Fischer; T Bieber; Y Li; H P Elsässer; T Kissel
Journal:  Pharm Res       Date:  1999-08       Impact factor: 4.200

8.  Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA nanoparticles in vivo.

Authors:  Assem-Galal Ziady; Christopher R Gedeon; Timothy Miller; William Quan; Jennifer M Payne; Susannah L Hyatt; Tamara L Fink; Osman Muhammad; Sharon Oette; Tomasz Kowalczyk; Murali K Pasumarthy; Robert C Moen; Mark J Cooper; Pamela B Davis
Journal:  Mol Ther       Date:  2003-12       Impact factor: 11.454

9.  Extensive distribution of liposomes in rodent brains and brain tumors following convection-enhanced delivery.

Authors:  Christoph Mamot; John B Nguyen; Micheal Pourdehnad; Piotr Hadaczek; Ryuta Saito; John R Bringas; Daryl C Drummond; Keelung Hong; Dmitri B Kirpotin; Tracy McKnight; Mitchel S Berger; John W Park; Krys S Bankiewicz
Journal:  J Neurooncol       Date:  2004-05       Impact factor: 4.130

10.  Long-term transgene expression in the central nervous system using DNA nanoparticles.

Authors:  David M Yurek; Anita M Fletcher; George M Smith; Kim B Seroogy; Assem G Ziady; Joseph Molter; Tomasz H Kowalczyk; Linas Padegimas; Mark J Cooper
Journal:  Mol Ther       Date:  2009-02-17       Impact factor: 11.454

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  3 in total

1.  Strategies to enhance the distribution of nanotherapeutics in the brain.

Authors:  Clark Zhang; Panagiotis Mastorakos; Miguel Sobral; Sneha Berry; Eric Song; Elizabeth Nance; Charles G Eberhart; Justin Hanes; Jung Soo Suk
Journal:  J Control Release       Date:  2017-07-21       Impact factor: 9.776

2.  Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors.

Authors:  Panagiotis Mastorakos; Clark Zhang; Eric Song; Young Eun Kim; Hee Won Park; Sneha Berry; Won Kyu Choi; Justin Hanes; Jung Soo Suk
Journal:  J Control Release       Date:  2017-07-08       Impact factor: 9.776

3.  Nanomaterials for convection-enhanced delivery of agents to treat brain tumors.

Authors:  Young-Eun Seo; Tom Bu; W Mark Saltzman
Journal:  Curr Opin Biomed Eng       Date:  2017-09-22
  3 in total

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