Efficient workflow for validating homology-independent targeted integration-mediated gene insertion in rod photoreceptor cells to treat dominant-negative mutations causing retinitis pigmentosa DOI Creative Commons
Akishi Onishi,

Yuji Tsunekawa,

Michiko Mandai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 9, 2023

Abstract Among the genome-editing methods for repairing disease-causing mutations resulting in dominant inhibition, homology-independent targeted integration (HITI)-mediated gene insertion of normal form causative is useful because it allows development mutation-agnostic therapeutic products. For rapid optimization and validation highly effective HITI-treatment constructs against dominant-negative inheritance inherited retinal dystrophy, we improved available both plasmid adeno-associated virus (AAV) vectors, established a workflow that uses vivo electroporation to verify efficacy. By targeting mouse Rhodopsin gene, derived construct which HITI-mediated occurs 80%-90% transduced rod photoreceptor cells. This suppressed degeneration induced visual restoration mutant mice. The rhodopsin were shown be AAV this construction Peripherin 2 gene. These findings suggest reported here may generation various target genes therapy

Language: Английский

Rare immune diseases paving the road for genome editing-based precision medicine DOI Creative Commons
Mara Pavel-Dinu, Šimon Borna, Rosa Bacchetta

et al.

Frontiers in Genome Editing, Journal Year: 2023, Volume and Issue: 5

Published: Feb. 8, 2023

Clustered regularly interspaced short palindromic repeats (CRISPR) genome editing platform heralds a new era of gene therapy. Innovative treatments for life-threatening monogenic diseases the blood and immune system are transitioning from semi-random addition to precise modification defective genes. As these therapies enter first-in-human clinical trials, their long-term safety efficacy will inform future generation editing-based medicine. Here we discuss significance Inborn Errors Immunity as disease prototypes establishing advancing precision We review feasibility clustered repeats-based platforms modify DNA sequence primary cells describe two emerging approaches treat RAG2 deficiency, immunodeficiency, FOXP3 regulatory disorder.

Language: Английский

Citations

7
Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F DOI Creative Commons

Sehar Riaz,

Saumil Sethna,

Todd Duncan

et al.

Molecular Therapy, Journal Year: 2023, Volume and Issue: 31(12), P. 3490 - 3501

Published: Oct. 20, 2023

Language: Английский

Citations

7
The Role of Pericytes in Inner Ear Disorders: A Comprehensive Review DOI Creative Commons
Antonino Maniaci, Marilena Briglia,

Fabio Allia

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 802 - 802

Published: Oct. 8, 2024

Inner ear disorders, including sensorineural hearing loss, Meniere’s disease, and vestibular neuritis, are prevalent conditions that significantly impact the quality of life. Despite their high incidence, underlying pathophysiology these disorders remains elusive, current treatment options often inadequate. Emerging evidence suggests pericytes, a type vascular mural cell specialized to maintain integrity function microvasculature, may play crucial role in development progression inner disorders. The pericytes present microvasculature both cochlea system, where they regulate blood flow, blood–labyrinth barrier, facilitate angiogenesis, provide trophic support neurons. Understanding valuable insights into lead novel diagnostic therapeutic strategies, improving standard living. This comprehensive review aims detailed overview highlighting anatomy physiology analyzing mechanisms contribute Furthermore, we explore potential pericyte-targeted therapies, antioxidant, anti-inflammatory, angiogenic approaches, as well gene therapy strategies.

Language: Английский

Citations

2
Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From the Liquid Biopsy to New Omics Technologies and Non-invasive Circulating Biomarkers DOI Open Access
Carmela Rita Balistreri

Published: June 29, 2022

The endothelium has multiple functions from maintaining vascular homeostasis, providing nutrition and oxygen to tissues, evocating inflammation, under adverse conditions, determining endo-thelial barrier disruption resulting in dysfunction. Endothelial dysfunction represents the typical condition associated with pathogenesis of all diseases cardiovascular system, as well other human body’s systems, also including sepsis, acute respiratory distress syn-drome COVID-19 distress. Such evidence is leading identifying potential bi-omarkers therapeutic targets for preserving, reverting, or restoring integrity functionality by early treating its Here, it stresses some strategies achieving these goals, even if diverse challenges exist require a significant bench work an in-creased number clinical studies.

Language: Английский

Citations

7
Optogenetics: Illuminating the Future of Hearing Restoration and Understanding Auditory Perception DOI
Namit Kant Singh, Balaji Ramamourthy, Neemu Hage

et al.

Current Gene Therapy, Journal Year: 2024, Volume and Issue: 24(3), P. 208 - 216

Published: Jan. 4, 2024

Abstract: Hearing loss is a prevalent sensory impairment significantly affecting communication and quality of life. Traditional approaches for hearing restoration, such as cochlear implants, have limitations in frequency resolution spatial selectivity. Optogenetics, an emerging field utilizing light-sensitive proteins, offers promising avenue addressing these revolutionizing rehabilitation. This review explores the methods introducing Channelrhodopsin- 2 (ChR2), key protein, into cells to enable optogenetic stimulation. Viral- mediated gene delivery widely employed technique optogenetics. Selecting suitable viral vector, adeno-associated viruses (AAV), crucial efficient cells. The ChR2 inserted vector through molecular cloning techniques, resulting introduced via direct injection or round window membrane delivery. allows expression subsequent light sensitivity targeted Alternatively, cell transfection non-viral approach cloned plasmid which then combined with agents like liposomes nanoparticles. mixture applied cells, facilitating entry DNA target enabling expression. Optogenetic stimulation using precise selective activation specific neurons response light, potentially overcoming current auditory prostheses. Moreover, optogenetics has broader implications understanding neural circuits involved processing behavior. combination techniques provides improving restoration strategies, offering potential enhanced resolution, selectivity, improved perception.

Language: Английский

Citations

1
Gene therapy for hereditary hearing loss DOI

Zeming Fu,

Liping Zhao,

Yingyuan Guo

et al.

Hearing Research, Journal Year: 2024, Volume and Issue: 455, P. 109151 - 109151

Published: Nov. 30, 2024

Language: Английский

Citations

1
Distributional comparison of different AAV vectors after unilateral cochlear administration DOI
Shuang Han, Zhijiao Xu, Shengyi Wang

et al.

Gene Therapy, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 14, 2023

Language: Английский

Citations

3
Gene Therapy for Rhodopsin Mutations DOI Open Access
Alfred S. Lewin,

Wayne C. Smith

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2022, Volume and Issue: 12(9), P. a041283 - a041283

Published: Aug. 8, 2022

Mutations in

Language: Английский

Citations

3
Implementing next-generation sequencing for diagnosis and management of hereditary hearing impairment: a comprehensive review DOI
Cheng‐Yu Tsai, Jacob Shujui Hsu, Pei‐Lung Chen

et al.

Expert Review of Molecular Diagnostics, Journal Year: 2024, Volume and Issue: 24(9), P. 753 - 765

Published: Aug. 28, 2024

Sensorineural hearing impairment (SNHI), a common childhood disorder with heterogeneous genetic causes, can lead to delayed language development and psychosocial problems. Next-generation sequencing (NGS) offers high-throughput screening high-sensitivity detection of etiologies SNHI, enabling clinicians make informed medical decisions, provide tailored treatments, improve prognostic outcomes.

Language: Английский

Citations

0
Somatic Genome Editing: Technical Challenges and Ethical Appraisal DOI
Francis J. O’Keeffe,

Aurélia Alphonse,

George L. Mendz

et al.

European Journal of Medical and Health Research, Journal Year: 2024, Volume and Issue: 2(3), P. 239 - 247

Published: May 1, 2024

The ability to modify the DNA sequences with molecular tools that employ nucleases has made it possible edit genomes. Somatic genome editing is procedure alter of somatic cells, making changes introduced into nucleotide sequence not inheritable. Powerful have been developed for therapeutic purposes correct monogenic inherited disorders often cause premature death and which effective treatment options are available. To ensure positive impact minimise potential harms these techniques, require understand their limits in addition apply values principles guide use. This study reviews technical challenges appraises Ethics its application.

Language: Английский

Citations

0