Recent Progress in the Endosomal Escape Mechanism and Chemical Structures of Polycations for Nucleic Acid Delivery

Mehta, Mohit J.; Kim, Hyun Jin; Lim, Sung Been; Naito, Mitsuru; Miyata, Kanjiro

doi:10.1002/mabi.202300366

Cited by 12 publications

(1 citation statement)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An improvement in photophysical properties of the RNA-binding dye will allow sequential imaging, which will allow for studying the evolution of the content distribution pattern as a function of time. Finally, we foresee that our method of content distribution assay based on superlocalization microscopy can be further adopted for estimating the efficiency of endosomal escape of cellular nanocarriers like lipid nanoparticles (LNPs) or vectors based on enveloped viruses which is still largely an empirical subject. − A reliable and straightforward measure of the content distribution between such nanocarriers and target vesicles (mimicking the endosome membrane) will be expected to better reflect its endosomal escape behavior and thus facilitate the rational design of the former.…”

Section: Discussionmentioning

confidence: 99%

A Fluorogenic Pseudoinfection Assay to Probe Transfer and Distribution of Influenza Viral Contents to Target Vesicles

Bhattacharya,

Bagheri,

Boxer

2024

Anal. Chem.

View full text Add to dashboard Cite

Fusion of enveloped viruses with endosomal membranes and subsequent release of the viral genome into the cytoplasm are crucial to the viral infection cycle. It is often modeled by performing fusion between virus particles and target lipid vesicles. We utilized fluorescence microscopy to characterize the kinetic aspects of the transfer of influenza viral ribonucleoprotein (vRNP) complexes to target vesicles and their spatial distribution within the fused volumes to gain deeper insight into the mechanistic aspects of endosomal escape. The fluorogenic RNA-binding dye QuantiFluor (Promega) was found to be well-suited for direct and sensitive microscopic observation of vRNPs which facilitated background-free detection and kinetic analysis of fusion events on a single particle level. To determine the extent to which the viral contents are transferred to the target vesicles through the fusion pore, we carried out virus-vesicle fusion in a side-by-side fashion. Measurement of the Euclidean distances between the centroids of superlocalized membrane and content dye signals within the fused volumes allowed determination of any symmetry (or the lack thereof) between them as expected in the event of transfer (or the lack thereof) of vRNPs, respectively. We found that, in the case of fusion between viruses and 100 nm target vesicles, ∼39% of the events led to transfer of viral contents to the target vesicles. This methodology provides a rapid, generic, and cell-free way to assess the inhibitory effects of antiviral drugs and therapeutics on the endosomal escape behavior of enveloped viruses.

show abstract

Section: Discussionmentioning

confidence: 99%

A Fluorogenic Pseudoinfection Assay to Probe Transfer and Distribution of Influenza Viral Contents to Target Vesicles

Bhattacharya,

Bagheri,

Boxer

2024

Anal. Chem.

View full text Add to dashboard Cite

show abstract

The Future of Nanomaterials Tackling the Challenge of Delivering Nucleic Acids to the Retina

Hurst,

Adams,

Schnichels

2024

Adv Funct Materials

View full text Add to dashboard Cite

Ocular gene therapy targets eye diseases at the genetic level. Systemic transport of nucleic acids to ocular tissues poses a significant challenge, as the effectiveness of crossing the blood‐retina barrier limits nucleic acid penetration. Therefore, local administration, such as topical, periocular, or intraocular, can improve the outcome of in vivo gene therapy by bypassing the first‐pass effect and minimizing the systemic toxic effects. The eye is an immune‐privileged organ with limited local immune response, making it an ideal candidate for local gene therapy. Ocular gene therapy offers a promising solution for the treatment of a wide range of retinal diseases including age‐related macular degeneration, diabetic retinopathy, retinitis pigmentosa, and Leber congenital amaurosis. Gene therapy enables replacement of mutated genes essential for visual function, delivery of genes expressing neurotrophic factors and anti‐apoptosis factors for retinal degeneration, and delivery of genes expressing anti‐angiogenic proteins for ocular neovascularization. This perspective discusses the potential of nanoparticles for nucleic acid delivery to the retina, explores challenges, and evaluates different delivery methods, including non‐viral agents such as liposomes and polymers. These nonviral agents present advantages over traditional viral vectors, showing promise in overcoming limitations and offering a viable option for retinal gene therapy.

show abstract

Nanoarchitectonics for Biomedical Research: Post‐Nanotechnology Materials Approach for Bio‐Active Application

Ariga

2024

Advanced NanoBiomed Research

View full text Add to dashboard Cite

Nanoarchitectonics, as a post‐nanotechnology concept, represents a methodology for the construction of functional materials employing atoms, molecules, and nanomaterials as essential components. The overarching objective of nanoarchitectonics is to develop functional systems comprising multiple functional units assembled in a hierarchical manner, as observed in biological systems. Nevertheless, the construction of such functional systems is a challenging endeavor. It would be prudent, therefore, to initially focus on the development of functional materials that interact with the complex functional structures of living organisms. Accordingly, this review article addresses the topic of nanoarchitecture as it pertains to biomedical applications. This article examines the current trends in research and presents examples of studies that support the concept of nanoarchitectonics and its applications in biomedical fields. The examples presented are as follows: i) molecular nanoarchitectonics developments, which are mainly based on molecular design and assembly; ii) material nanoarchitectonics examples, which are mainly based on material design using nanomaterials as components; and iii) biomedical applications with porous materials, which will be summarized under the heading of pore‐engineered nanoarchitectonics due to their special structure. Finally, the review provides an overview of these examples and discusses future prospects.

show abstract

Recent Progress in the Endosomal Escape Mechanism and Chemical Structures of Polycations for Nucleic Acid Delivery

Cited by 12 publications

References 128 publications

A Fluorogenic Pseudoinfection Assay to Probe Transfer and Distribution of Influenza Viral Contents to Target Vesicles

A Fluorogenic Pseudoinfection Assay to Probe Transfer and Distribution of Influenza Viral Contents to Target Vesicles

The Future of Nanomaterials Tackling the Challenge of Delivering Nucleic Acids to the Retina

Nanoarchitectonics for Biomedical Research: Post‐Nanotechnology Materials Approach for Bio‐Active Application

Contact Info

Product

Resources

About