Nature Protocols, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 15, 2024
Language: Английский
Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 13, 2024
Abstract Engineered virus-like particles (eVLPs) are promising vehicles for transient delivery of proteins and RNAs, including gene editing agents. We report a system the laboratory evolution eVLPs that enables discovery eVLP variants with improved properties. The uses barcoded guide RNAs loaded within DNA-free eVLP-packaged cargos to uniquely label each variant in library, enabling identification desired following selections applied this mutate select capsids production properties or transduction efficiencies human cells. By combining beneficial capsid mutations, we developed fifth-generation (v5) eVLPs, which exhibit 2–4-fold increase cultured mammalian cell potency compared previous-best v4 eVLPs. Analyses v5 suggest these mutations optimize packaging ribonucleoprotein rather than native viral genomes substantially alter structure. These findings potential support development
Language: Английский
Citations
7
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: Dec. 20, 2024
Abstract CRISPR-based gene editing technology theoretically allows for precise manipulation of any genetic target within living cells, achieving the desired sequence modifications. This revolutionary advancement has fundamentally transformed field biomedicine, offering immense clinical potential treating and correcting disorders. In treatment most diseases, genome that avoids generation mixed byproducts is considered ideal approach. article reviews current progress base editors prime editors, elaborating on specific examples their applications in therapeutic field, highlights opportunities improvement. Furthermore, we discuss performance these technologies terms safety efficacy applications, analyze latest advancements directions could influence future development technologies. Our goal to outline relevance this rapidly evolving scientific preview a roadmap successful DNA therapies hereditary or idiopathic diseases.
Language: Английский
Citations
6
Molecular Therapy — Nucleic Acids, Journal Year: 2024, Volume and Issue: 35(4), P. 102375 - 102375
Published: Oct. 30, 2024
Language: Английский
Citations
4
Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 6, 2024
Language: Английский
Citations
4
Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 970 - 985
Published: Jan. 10, 2025
Language: Английский
Citations
0
Methods in enzymology on CD-ROM/Methods in enzymology, Journal Year: 2025, Volume and Issue: unknown, P. 419 - 436
Published: Jan. 1, 2025
Language: Английский
Citations
0
Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 27, 2025
ABSTRACT Genetic diseases have long posed significant challenges, with limited breakthroughs in treatment. Recent advances gene editing technologies offer new possibilities therapy for the treatment of inherited disorders. However, traditional methods limitations that hinder their potential clinical use, such as capabilities and production unintended byproducts. To overcome these limitations, prime (PE) has been developed a powerful tool precise efficient genome modification. In this review, we provide an overview latest advancements PE its applications Furthermore, examine current delivery vehicles employed delivering systems vitro vivo, analyze respective benefits limitations. Ultimately, discuss challenges need to be addressed fully unlock remission or cure genetic diseases.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2835 - 2835
Published: March 21, 2025
RyR1-related myopathies (RyR1-RMs) include a wide range of genetic disorders that result from mutations in the RYR1 gene. Pathogenic variants lead to defective intracellular calcium homeostasis and muscle dysfunction. Fixing leaks by stabilizing RyR1 channel has been identified as promising therapeutic target. Gene therapy via prime editing also holds great promise it can cure diseases correcting mutations. However, more than 700 have gene, universal treatment would be suitable solution for patients. Our investigation into RyR1-S2843A mutation yielded results. Using leak assay, we determined S2843A was protective when combined with pathogenic significantly reduced Ca2+ channel. study demonstrated efficiently introduce mutation. In vitro experiments using RNA electroporation components human myoblasts achieved 31% introduction this This article lays foundation new approach RyR1-RM, where unique once-in-a-lifetime could potentially universally applied all patients leaky
Language: Английский
Citations
0
Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101636 - 101636
Published: April 1, 2025
Language: Английский
Citations
0
Human Gene Therapy, Journal Year: 2025, Volume and Issue: unknown
Published: April 28, 2025
The advent of genome editing has kindled the hope to cure previously uncurable, life-threatening genetic diseases. However, whether this promise can be ultimately fulfilled depends on how efficiently gene agents delivered therapeutically relevant cells. Over time, viruses have evolved into sophisticated, versatile, and biocompatible nanomachines that engineered shuttle payloads specific cell types. Despite advances in safety selectivity, long-term expression sustained by viral vectors remains a cause for concern. Cell-derived vesicles (CDVs) are gaining traction as elegant alternatives. CDVs encompass extracellular (EVs), diverse set intrinsically low-immunogenic membranous nanoparticles, virus-like particles (VLPs), bioparticles with scaffold envelope structures, but devoid material. Both EVs VLPs deliver ribonucleoprotein cargo target cytoplasm, ensuring machinery is only transiently active thereby increasing its safety. In review, we explore natural diversity their potential delivery clustered regularly interspaced short palindromic repeats (CRISPR) machinery. We illustrate different strategies optimization CDV loading retargeting, highlighting versatility tunability these vehicles. Nonetheless, lack robust standardized protocols production, purification, quality assessment still hinders widespread adoption further CRISPR-based therapies advanced "living drugs." believe collective, multifaceted effort urgently needed address critical issues unlock full genome-editing technologies yield safe, easy-to-manufacture, pharmacologically well-defined therapies. Finally, discuss current clinical landscape lung-directed cystic fibrosis could drive significant breakthroughs vivo disease.
Language: Английский
Citations
0