Abstract
Gene therapy is a critical tool for the treatment of monogenic retinal diseases. However, the limited vector capacity of the current benchmark delivery strategy, adeno-associated virus (AAV), makes development of larger capacity alternatives, such as compacted DNA nanoparticles (NPs), critical. Here we conduct a side-by-side comparison of self-complementary AAV and CK30PEG NPs using matched ITR plasmids. We report that although AAVs are more efficient per vector genome (vg) than NPs, NPs can drive gene expression on a comparable scale and longevity to AAV. We show that subretinally injected NPs do not leave the eye while some of the AAV-injected animals exhibited vector DNA and GFP expression in the visual pathways of the brain from PI-60 onward. As a result, these NPs have the potential to become a successful alternative for ocular gene therapy, especially for the multitude of genes too large for AAV vectors.
Highlights
Recombinant adeno-associated viruses (AAVs) have been highly successful for ocular gene therapy due to their safety and ability to drive long-term gene expression [1,2,3,4]
Identical plasmids were used to produce AAVs or acetate-formulated CK30PEG10K NPs (AAV2-chicken b-actin (CBA)-GFP, NPCBA-GFP, AAV5-mouse opsin promoter (MOP)-GFP, NP-MOP-GFP), and in some experiments uncompacted plasmids were used as controls
Eyes were collected at post-injection day (PI-) 14 and GFP message levels were analyzed by qRT-PCR
Summary
Recombinant adeno-associated viruses (AAVs) have been highly successful for ocular gene therapy due to their safety and ability to drive long-term gene expression [1,2,3,4]. As a result of these trials and numerous animal studies [3,8] AAV is considered the current leading vector system for ocular gene therapy. While AAVs are well-positioned to remain key players for ocular gene therapy, their limited vector capacity prevents them from being useful for the delivery of large genes, such as ABCA4 and USH2A. Recent studies have experimented with ways to increase AAV capacity [13,14], the results are controversial and inconclusive underscoring the need for alternative tools for ocular gene therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
