Are we prepared to deliver gene‐targeted therapies for rare diseases?

Yu, Timothy W.; Green, Robert C; MacKenzie, Tippi C.; Wasserstein, Melissa P.; Casini, Michèle; Gold, Nina B.; Kennedy, Annie; Kishnani, Priya S.; Might, Matthew; Brooks, P J; Morris, Jill A.; Parisi, Melissa A.; Urv, Tiina K.

doi:10.1002/ajmg.c.32029

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…It will also be interesting to see whether the ratios shift. For example, specific, genetic therapies may lead to much longer and different lives for those affected by many congenital and early-onset genetic conditions (Yu et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Age‐related survey of clinical genetics literature and related resources

Solomon

Solomon²

2023

American J of Med Genetics Pt C

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Genetic conditions affect people throughout their entire lifespan; however, many clinical geneticists focus on the care of pediatric individuals. We analyzed the medical literature and related resources to help assess to what extent adults with genetic diseases were represented. This included general literature searches of PubMed (from 2001 through 2022), specific databases (the FDA orphan drug list and the Clinical Genomic Database) related to management and direct treatment of genetic conditions, and textbooks and morphology guides relevant to the diagnosis of genetic conditions. In the field of genetics/genomics in general, we overall detected a statistically significant emphasis on pediatric populations in the medical literature compared to select other disciplines and compared with the global population distribution. Clinical genetics articles about adults tended to focus on younger adult ages. In clinical genetics, management and treatments, as well as illustrations in several educational/diagnostic resources tended to focus on pediatric populations.

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Section: Discussionmentioning

confidence: 99%

Age‐related survey of clinical genetics literature and related resources

Solomon

Solomon²

2023

American J of Med Genetics Pt C

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“…ABX1100, a Centyrin-siRNA conjugate, targets the Gys1 gene in muscles and is used for treating Pompe disease. This novel approach aims to reduce glycogen accumulation in muscles and received FDA designation in August 2022. , Additionally, chemically modified RNAs have shown promise in other disorders such as Hemophilia A and B, Machado-Joseph disease (MJD), transmembrane channel-like protein 1 (Tmc1)-related deafness, cystic fibrosis, DMD, and Williams-Beuren syndrome (WBS). These applications highlight the broad potential of chemically modified RNAs in various therapeutic contexts.…”

Section: Chemical Modification-assisted Better Rna Therapeuticsmentioning

confidence: 99%

Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration. CONTENTS1. Introduction 930 2. Current Status and Challenges of RNA Therapeutics in Clinics 933 2.1. Molecular Mechanisms and Clinical Research Progress of RNAs 934 2.1.1. ASO 934 2.1.2. siRNA 934 2.1.3. Aptamer 936 2.1.4. mRNA 936 2.1.5. RNA Therapeutics on the Cusp of Clinical Breakthroughs 938 2.2. Major Challenges of Current RNA Therapeutics in Clinics 940 2.

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“…This gap in physician knowledge is also increasing because of a rapid increase in the number of investigational new drug applications and approvals for new gene-based therapeutics (Fig. 2 ) 165 . Recently several groups have described AI-assisted clinical decision support tools for therapeutic interventions for rare genetic diseases 14 , 165 .…”

Section: Increasing Use Of Artificial Intelligence (Ai) In Urgsmentioning

confidence: 99%

“…2 ) 165 . Recently several groups have described AI-assisted clinical decision support tools for therapeutic interventions for rare genetic diseases 14 , 165 .…”

Section: Increasing Use Of Artificial Intelligence (Ai) In Urgsmentioning

confidence: 99%

Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review

Kingsmore,

Nofsinger,

Ellsworth

2024

npj Genom. Med.

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Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases for ICU patients. In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, and net healthcare costs were reduced by $14,265 per child tested by URGS, RGS, or RES. URGS outperformed RGS and RES with faster time to diagnosis, and higher rate of diagnosis and clinical utility. Diagnostic and clinical outcomes will improve as methods evolve, costs decrease, and testing is implemented within precision medicine delivery systems attuned to ICU needs. URGS, RGS, and RES are currently performed in <5% of the ~200,000 children likely to benefit annually due to lack of payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition of possible genetic diseases, and current formatting as tests rather than as a rapid precision medicine delivery system. The gap between actual and optimal outcomes in children in ICUs is currently increasing since expanded use of URGS, RGS, and RES lags growth in those likely to benefit through new therapies. There is sufficient evidence to conclude that URGS, RGS, or RES should be considered in all children with diseases of uncertain etiology at ICU admission. Minimally, diagnostic URGS, RGS, or RES should be ordered early during admissions of critically ill infants and children with suspected genetic diseases.

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Are we prepared to deliver gene‐targeted therapies for rare diseases?

Cited by 11 publications

References 10 publications

Age‐related survey of clinical genetics literature and related resources

Age‐related survey of clinical genetics literature and related resources

Chemically Modified Platforms for Better RNA Therapeutics

Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review

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