The promise of cancer gene therapeutics is hampered by difficulties in the in vivo delivery to the targeted tumor cells, and systemic delivery remains to be the biggest challenge to be overcome. Here, we concentrate on systemic in vivo gene delivery for cancer therapy using nonviral vectors. In this review, we summarize the existing delivery barriers together with the requirements and strategies to overcome these problems. We will also introduce the current progress in the design of nonviral vectors, and briefly discuss their safety issues.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University, Baltimore, MD; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Chemical & Biomolecular Engineering and Materials Science & Engineering, Johns Hopkins University, Baltimore, MD; Departments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD. Electronic address:
Current treatments for retinal and choroidal neovascular diseases suffer from insufficient durability, including anti-vascular endothelial growth factor-A (VEGF-A) agents. It is, therefore, of interest to explore alternative methods that could allow for robust improvement in visual acuity with fewer injections required. Amongst various pre-clinical and clinical studies in the literature, a promising approach is the use of suprachoroidal injection with viral and non-viral gene delivery vectors.
CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) has revolutionized gene editing tools and paved the way for innovations in medical research for disease diagnosis and treatment. However, better specificity and efficient delivery of this gene machinery make it challenging to successfully edit genes for treating various diseases. This is mainly due to cellular barriers, instability in biological environments, and various off-target effects that prohibit safe and efficient delivery under in vivo conditions.
Leber's congenital amaurosis (LCA) represents a set of rare and pervasive hereditary conditions of the retina that cause severe vision loss starting in early childhood. Targeted treatment intervention has become possible thanks to recent advances in understanding LCA genetic basis. While viral vectors have shown efficacy in gene delivery, they present challenges related to safety, low cargo capacity, and the potential for random genomic integration.
Over the past years, many significant advances have been made in the field of gene therapy and shown promising results in clinical trials conducted. Gene therapy aims at modifying or replacing a defective, inefficient, or nonfunctional gene with a healthy, functional gene by administration of genome material into the cell to cure genetic diseases. Various methods have been devised to do this by using several viral and non-viral vectors which are either administered by in vivo or ex vivo technique.
mRNA is crucial for various biomedical applications, but safe and efficient delivery into target cells is key for its effectiveness.
A new ternary delivery system was developed using linear poly(β-amino ester)s (LPAEs) coated with hyaluronic acid (HA), which significantly improves mRNA transfection efficiency and cell viability.
The HA coating enhances the properties of the polyplexes, increasing their ability to interact with cell membranes, suggesting this method could benefit other non-viral mRNA delivery systems.
