Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles

Sun, Da; Schur, Rebecca; Sears, Avery E.; Gao, Songqi; Vaidya, Amita; Sun, Wenyu; Maeda, Akiko; Kern, Timothy S.; Palczewski, Krzysztof; Lü, Zheng Rong

doi:10.1016/j.ymthe.2019.09.010

Cited by 35 publications

(42 citation statements)

References 47 publications

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“…The therapeutics effects lasted for at least 120 days [ 94 ]. The therapeutic potential of ECO/pDNA nanoparticles in the treatment of visual dystrophies was also confirmed by further research [ 95 , 96 ]. Malamas et al [ 90 ] optimized the amphiphilic cationic lipid carriers by evaluation of the role of protonatable amine numbers and pKa of the cationic head group, the degree of unsaturation of the bis-hydrophobic tails and the presence of histidine residues as an amino acid linker.…”

Section: Sequence-defined Macromolecular Carriersmentioning

confidence: 72%

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

Wang

Wagner

2020

Pharmaceutics

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In nature, genomes have been optimized by the evolution of their nucleic acid sequences. The design of peptide-like carriers as synthetic sequences provides a strategy for optimizing multifunctional targeted nucleic acid delivery in an iterative process. The optimization of sequence-defined nanocarriers differs for different nucleic acid cargos as well as their specific applications. Supramolecular self-assembly enriched the development of a virus-inspired non-viral nucleic acid delivery system. Incorporation of DNA barcodes presents a complementary approach of applying sequences for nanocarrier optimization. This strategy may greatly help to identify nucleic acid carriers that can overcome pharmacological barriers and facilitate targeted delivery in vivo. Barcode sequences enable simultaneous evaluation of multiple nucleic acid nanocarriers in a single test organism for in vivo biodistribution as well as in vivo bioactivity.

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Section: Sequence-defined Macromolecular Carriersmentioning

confidence: 72%

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

Wang

Wagner

2020

Pharmaceutics

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“…These so-called ECO nanoparticles consist of a protonable ethylenediamine (E) head group, two cysteine (C) functional linkers, and two oleoyl (O) lipophilic tails [ 43 ]. In the eye, these nanoparticles, self-assembled by the multifunctional pH-sensitive amino lipid ECO and a therapeutic bovine rhodopsin promoter-driven ABCA4 plasmid, delayed the phenotype of an Abca4 −/− Stargardt mouse model for at least six months [ 44 ]. The 16 kb plasmid is the largest reported for non-viral gene therapy in the eye.…”

Section: Nanoparticlesmentioning

confidence: 99%

The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases

Toualbi

Toms

Moosajee

2021

IJMS

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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.

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“…The promising drug release characteristics of nanodimensional delivery systems make them a potent tool in gene therapy, where the genetic characteristics of the patient can be targeted specifically during cancer treatment 1‐4 . This concept may be possible by using suitable biotherapeutics, such as siRNA that can be encapsulated in a drug delivery vehicle and administrated to the target site without compromising their ability to deliver drug at the site of target 4‐6 . Originally the viral method of delivery was used but due to its limitations like the use of viruses in production on a large scale, toxicity and immunogenicity, the method is not preferred and a need for a new method is essential 7 (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…Originally the viral method of delivery was used but due to its limitations like the use of viruses in production on a large scale, toxicity and immunogenicity, the method is not preferred and a need for a new method is essential 7 (Table 1). 6,8‐10 Different types of nanoparticulate delivery systems, like lipid‐based vesicles, ketals nucleoside lipid nanoparticles (NPs), cell penetrating peptides NPs, polymersomes, chitosan‐based NPs have been utilized by researchers to deliver siRNA for cancer treatment 4,5,11‐15 . The process by which the target gene expression is reduced by siRNA is known as RNA interference (or RNAi).…”

Section: Introductionmentioning

confidence: 99%

“…6,[8][9][10] Different types of nanoparticulate delivery systems, like lipid-based vesicles, ketals nucleoside lipid nanoparticles (NPs), cell penetrating peptides NPs, polymersomes, chitosan-based NPs have been utilized by researchers to deliver siRNA for cancer treatment. 4,5,[11][12][13][14][15] The process by which the target gene expression is reduced by siRNA is known as RNA interference (or RNAi). RNAi is a powerful process, which can be used to knockdown abnormal gene expression, especially in many cancers where the perturbed gene expression can lead to the growth and metastasis of cancer cells.…”

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confidence: 99%

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Nanoparticulate RNA delivery systems in cancer

et al. 2020

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Background: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy). Recent findings: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/ shRNA, will assist in developing improved drug delivery strategies in basic and clinical research. Conclusion: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades.

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Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles

Cited by 35 publications

References 47 publications

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases

Nanoparticulate RNA delivery systems in cancer

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