Next generation sequencing: Coping with rare genetic diseases in China

Zhong

et al. 2020

Molec Gen & Gen Med

In prenatal diagnosis, chromosomal aberrations, such as aneuploidies and copy number variation (CNV), are one of the important reasons for ultrasound structural abnormalities and products of conceptions (POC). CNVs are pervasive in human genome and account for a large fraction of the population diversity in humans (Girirajan, Campbell, & Eichler, 2011). Many CNVs located in specific genome regions also have clinical significance or have strong associations with well-characterized genomic disorders, such as 22q11 deletion syndrome (Velocardiofacial/DiGeorge syndrome; Faas et al.,

Section: Discussionmentioning

confidence: 99%

REDBot: Natural language process methods for clinical copy number variation reporting in prenatal and products of conception diagnosis

Zhong

et al. 2020

Molec Gen & Gen Med

“…This is particularly true for the assumed vast majority of classifiable rare diseases that have a genetic cause, with key developments the rapid discovery of novel causative mutations for rare diseases by massively parallel sequencing [ 23 ] and adoption of global variant database and nomenclature standards to make the information universally accessible and interpretable [ 14 , 19 ]. While one of the major contributions of rapid variant discovery to reducing the global burden of disease is seen in rare disease prevention [ 24 ], it likewise provides the foundation for stratified if not personalized rare disease treatments by gene therapy.…”

Section: Rare Diseases: Towards Curative Treatmentsmentioning

confidence: 99%

Rare Opportunities: CRISPR/Cas-Based Therapy Development for Rare Genetic Diseases

2019

Rare diseases pose a global challenge, in that their collective impact on health systems is considerable, whereas their individually rare occurrence impedes research and development of efficient therapies. In consequence, patients and their families are often unable to find an expert for their affliction, let alone a cure. The tide is turning as pharmaceutical companies embrace gene therapy development and as serviceable tools for the repair of primary mutations separate the ability to create cures from underlying disease expertise. Whereas gene therapy by gene addition took decades to reach the clinic by incremental diseasespecific refinements of vectors and methods, gene therapy by genome editing in its basic form merely requires certainty about the causative mutation. Suddenly we move from concept to trial in 3 years instead of 30: therapy development in the fast lane, with all the positive and negative implications of the phrase. Since their first application to eukaryotic cells in 2013, the proliferation and refinement in particular of tools based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPRassociated protein (Cas) prokaryotic RNA-guided nucleases has prompted a landslide of therapy-development studies for rare diseases. An estimated thousands of orphan diseases are up for adoption, and legislative, entrepreneurial, and research initiatives may finally conspire to find many of them a good home. Here we summarize the most significant recent achievements and remaining hurdles in the application of CRISPR/Cas technology to rare diseases and take a glimpse at the exciting road ahead. Marina Kleanthous and Carsten W. Lederer contributed equally to this review.

“…There are few, if any, therapy options available for most hereditary diseases [17]. As a result, gene-editing tools such as transcription activator-like effector nucleases (TALENs), zinc finger nucleases (ZFNs), and meganucleases, as well as CRISPR (clustered regulatory interspaced short palindromic repeats)-Cas9 (CRISPR-associated enzyme), have sparked a significant interest.…”

Section: Introductionmentioning

confidence: 99%

CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease

et al. 2022

Parkinson’s disease (PD) and other chronic and debilitating neurodegenerative diseases (NDs) impose a substantial medical, emotional, and financial burden on individuals and society. The origin of PD is unknown due to a complex combination of hereditary and environmental risk factors. However, over the last several decades, a significant amount of available data from clinical and experimental studies has implicated neuroinflammation, oxidative stress, dysregulated protein degradation, and mitochondrial dysfunction as the primary causes of PD neurodegeneration. The new gene-editing techniques hold great promise for research and therapy of NDs, such as PD, for which there are currently no effective disease-modifying treatments. As a result, gene therapy may offer new treatment options, transforming our ability to treat this disease. We present a detailed overview of novel gene-editing delivery vehicles, which is essential for their successful implementation in both cutting-edge research and prospective therapeutics. Moreover, we review the most recent advancements in CRISPR-based applications and gene therapies for a better understanding of treating PD. We explore the benefits and drawbacks of using them for a range of gene-editing applications in the brain, emphasizing some fascinating possibilities.