Abstract
Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs.
Highlights
Inherited retinal diseases (IRDs) are a group of genetically and phenotypically heterogeneous conditions affecting around one in 1000 people worldwide, with degeneration of the retina resulting in progressive loss of vision [1]
This review will describe the range of approaches for non-viral gene augmentation therapy that have been investigated for IRD treatment in the literature
Naash’s group have used compacted rod-shaped DNA nanoparticles formulated with 30-mer poly-L-lysin peptides conjugated to polyethylene glycol 10,000K (CK30PEG) in a number of investigations; they have successfully shown efficient transfection of photoreceptors and retinal pigment epithelium (RPE) cells, which improved the phenotype of several retinal mouse disease models such as retinitis pigmentosa [35] and Leber congenital amaurosis, with up to two years of persistent transgene expression [27]
Summary
Inherited retinal diseases (IRDs) are a group of genetically and phenotypically heterogeneous conditions affecting around one in 1000 people worldwide, with degeneration of the retina resulting in progressive loss of vision [1]. The development of alternative vectors is crucial to broaden the gene therapy options for IRDs. Non-viral gene delivery systems are typically composed of the required nucleic acid (e.g., plasmid) complexed with a vehicle, such as cationic lipids or polymers, to aid cell entry. There has been a growing interest in non-viral gene therapies over the years, with a number of clinical trials completed and ongoing to treat a range of diseases, including cystic fibrosis and several types of cancer [3] They may address the disadvantages of viral vectors, non-viral methods have not demonstrated transfection efficiencies in the retina comparable to AAV, and a number of chemical and physical-based strategies are under development to overcome this limitation. This review will describe the range of approaches for non-viral gene augmentation therapy that have been investigated for IRD treatment in the literature
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
