How Advanced are Nanocarriers for Effective Subretinal Injection? DOI Creative Commons

Jiaxin Guan,

Yanling Wang,

Jialin Wang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 9273 - 9289

Published: Sept. 1, 2024

Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment neovascular age-associated macular degeneration (nAMD) sub-macular hemorrhage (SMH) caused by nAMD, as well various types hereditary retinopathies (IRD) such Stargardt's disease (STGD), retinitis pigmentosa (RP), series fundus diseases Leber's congenital dark haze (LCA), choroidal defects, etc. The carriers SR are divided into viral non-viral vectors. amaurosis agenesis, other also treated using injection. vectors two categories: Viral traditional class that have extensively studied in clinical treatment, but they still many limitations cannot be ignored, poor reproduction efficiency, small loading genes, triggering immune reactions. With rapid development nanotechnology diseases, nanovectors become research hotspot field Nanocarriers numerous attractive properties low immunogenicity, robust capacity, stable structure, easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, more flexible indications. In recent years, there growing interest nanocarriers, which led to significant advancements diseases. not only successfully addressed problems failed overcome introduced new possibilities certain classical types. offer undeniable advantages over This review discusses subretinal (SR) injection, current status research, hotspots gene therapy with It focuses on latest progress nanocarriers enumerates future perspectives lesions. Furthermore, this covers highlights value nanocarrier-mediated disorders. Overall, it provides theoretical basis application

Language: Английский

Optimization strategies and advances in the research and development of AAV‐based gene therapy to deliver large transgenes DOI Creative Commons
Valeria V. Kolesnik,

Ruslan F. Nurtdinov,

Ezekiel S. Oloruntimehin

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

Adeno-associated virus (AAV)-based therapies are recognized as one of the most potent next-generation treatments for inherited and genetic diseases. However, several biological technological aspects AAV vectors remain a critical issue their widespread clinical application. Among them, limited capacity genome significantly hinders development AAV-based gene therapy. In this context, genetically modified transgenes compatible with opening up new opportunities unlimited many disorders. Recent advances in de novo protein design remodelling paving way new, more efficient targeted therapeutics. Using computational tools, expression cassette transgenic DNA can be split, miniaturized, shuffled or created from scratch to mediate transfer into cells. review, we highlight recent therapy focus on its use translational research. We summarize research therapy, an emphasis large (>4.8 kb) optimizing strategies applied by biomedical companies pipeline. critically discuss prospects treatment some emerging challenges. anticipate that continued novel tools will lead rapid basic studies.

Language: Английский

Citations

12
AAV‐mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives DOI Creative Commons
Liyan Zhang, Fangzhi Tan, Jieyu Qi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract Hereditary deafness is the most prevalent sensory deficit disorder, with over 100 identified deafness‐related genes. Clinical treatment options are currently limited to external devices like hearing aids and cochlear implants. Gene therapy has shown promising results in various genetic disorders emerged as a potential for hereditary deafness. It successfully restored function >20 types of model mice can almost completely cure patients autosomal recessvie 9 (DFNB9) caused by OTOFERLIN ( OTOF ) mutation, thus serving translational paradigm gene other forms However, due complexity inner ear structure, diverse nature genes, variations transduction efficiency among different cells targeted adeno‐associated virus (AAV), precision approaches required This review provides comprehensive overview deafness, including preclinical studies recent research advancements this field well challenges associated AAV‐mediated therapy.

Language: Английский

Citations

10
The Role of Visual Electrophysiology in Systemic Hereditary Syndromes DOI Open Access
Minzhong Yu,

Emile R. Vieta-Ferrer,

Anas Bakdalieh

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 957 - 957

Published: Jan. 23, 2025

Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal (mfERG), evoked potentials (VEP), electrooculography (EOG) offer insights into retinal optic nerve function, often detecting abnormalities before symptoms manifest. In loss like Refsum disease, Usher syndrome, Wolfram facilitates detection early changes that precede onset symptoms. For disorders maternally-inherited diabetes deafness (MIDD), Kearns–Sayre neuropathy, ataxia, retinitis pigmentosa (NARP) these tests can be useful characterizing degeneration neuropathy. obesity syndromes, including Alström Bardet-Biedl Cohen progressive hallmark feature. Electrophysiological techniques aid pinpointing dysfunction tracking disease progression. Other abetalipoproteinemia (Bassen–Kornzweig syndrome), Alagille Cockayne mucopolysaccharidosis, Senior–Løken exhibit significant ocular involvement evaluated using methods. underscores role diagnosing monitoring across range potentially offering diagnosis, progression, management.

Language: Английский

Citations

1
Multiple nucleotide variants in genetic diagnosis: implications from 11,467 cases of hearing loss DOI

Fandi Ai,

Jiayi Zeng, Qian Zhang

et al.

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Retina-directed gene therapy: Achievements and remaining challenges DOI

Josef Biber,

Catharina Gandor,

Elvir Bećirović

et al.

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108862 - 108862

Published: April 1, 2025

Language: Английский

Citations

0
Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins DOI Creative Commons
Pedro De‐la‐Torre, Haosheng Wen,

Joseph Brower

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Protocadherin-15 is a core protein component of inner-ear hair-cell tip links pulling on transduction channels essential for hearing and balance. defects can result in non-syndromic deafness or Usher syndrome type 1F (USH1F) with loss, balance deficits, progressive blindness. Three rationally engineered shortened versions protocadherin-15 (mini-PCDH15s) amenable gene therapy have been used to rescue function USH1F mouse models. Two successfully partially hearing, while another one fails. Here we show that despite varying levels rescue, all three mini-PCDH15 mechanotransduction. Negative-stain electron microscopy shows form dimers like the wild-type protein, crystal structures some fragments these properly fold bind calcium ions function. In contrast, simulations predict distinct elasticities nano differential scanning fluorimetry differences melting temperature measurements. Our data suggest elasticity thermal stability are key determinants sustained by mini-PCDH15s.

Language: Английский

Citations

0
How Advanced are Nanocarriers for Effective Subretinal Injection? DOI Creative Commons

Jiaxin Guan,

Yanling Wang,

Jialin Wang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 9273 - 9289

Published: Sept. 1, 2024

Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment neovascular age-associated macular degeneration (nAMD) sub-macular hemorrhage (SMH) caused by nAMD, as well various types hereditary retinopathies (IRD) such Stargardt's disease (STGD), retinitis pigmentosa (RP), series fundus diseases Leber's congenital dark haze (LCA), choroidal defects, etc. The carriers SR are divided into viral non-viral vectors. amaurosis agenesis, other also treated using injection. vectors two categories: Viral traditional class that have extensively studied in clinical treatment, but they still many limitations cannot be ignored, poor reproduction efficiency, small loading genes, triggering immune reactions. With rapid development nanotechnology diseases, nanovectors become research hotspot field Nanocarriers numerous attractive properties low immunogenicity, robust capacity, stable structure, easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, more flexible indications. In recent years, there growing interest nanocarriers, which led to significant advancements diseases. not only successfully addressed problems failed overcome introduced new possibilities certain classical types. offer undeniable advantages over This review discusses subretinal (SR) injection, current status research, hotspots gene therapy with It focuses on latest progress nanocarriers enumerates future perspectives lesions. Furthermore, this covers highlights value nanocarrier-mediated disorders. Overall, it provides theoretical basis application

Language: Английский

Citations

0