Duke Genomic Seminar Series

A platform approach to develop and deploy CRISPR-Cas based experimental therapies for inborn errors of immunity in an academic/nonprofit setting

Thursday, February 8 | 2-3 p.m. ET | Bryan Neurobiology Research Building, Rm 103

Speaker: Fyodor Urnov, PhD
Professor of Molecular & Cellular Biology, University of California, Berkeley
Director of Technology & Translation, Innovative Genomics Institute

The vast majority of diseases clinically tractable by genome editing using current-state technology are not the targets of active preclinical or clinical development. Addressing this issue will require more involvement of the academic/nonprofit sector, but despite an existing charted path for advancing genome editing of specific cell types and tissues (such as T cells, hematopoietic stem cells, the liver, and the retina) to the clinic, there presently is only one open US IND for genome editing by an all-academic group. A key reason is that the current manufacturing, regulatory, and healthcare economics environment is not configured to maximize clinical impact of a technology like CRISPR-Cas. Under the framework that exists today, a pediatric patient newly diagnosed with a terminal illness such as a severe inborn error of immunity due to a never-before-seen but clinically editable mutation and a life expectancy of < 1 yr will have to wait ~3.5 years until a gene editing medicine is engineered, tested, and manufactured at an approximate total cost of $9m. An actionable path through this status quo is to develop and clinically derisk a dedicated nonclinical development path for use in academic/nonprofit settings in N=1/rare situations of dire medical need. From a technology standpoint, this will require comprehensive leveraging of the intrinsically platform nature of CRISPR-Cas gene editing. The Innovative Genomics Institute in close partnership with clinicians at UCSF and UCLA is developing such a platform focused on inborn errors of immunity, where ca 112,000 known patients suffering from 505 currently known diseases lack even a single open trial for genome editing open at the present time.

To learn more, visit Duke’s Genomic Seminar Series page.

Please note: This seminar series occurs quarterly with some events occurring virtually only and others in-person with streaming options.

Clinician adherence to pharmacogenomics prescribing recommendations in clinical decision support alerts

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Jenny Q Nguyen, Kristine R Crews, Ben T Moore, Nancy M Kornegay, Donald K Baker, Murad Hasan, Patrick K Campbell, Shannon M Dean, Mary V Relling , James M Hoffman, Cyrine E Haidar

Abstract

Thoughtful integration of interruptive clinical decision support (CDS) alerts within the electronic health record is essential to guide clinicians on the application of pharmacogenomic results at point of care. St. Jude Children’s Research Hospital implemented a preemptive pharmacogenomic testing program in 2011 in a multidisciplinary effort involving extensive education to clinicians about pharmacogenomic implications. We conducted a retrospective analysis of clinicians’ adherence to 4783 pharmacogenomically guided CDS alerts that triggered for 12 genes and 60 drugs. Clinicians adhered to the therapeutic recommendations provided in 4392 alerts (92%). In our population of pediatric patients with catastrophic illnesses, the most frequently presented gene/drug CDS alerts were TPMT/NUDT15 and thiopurines (n = 3850), CYP2D6 and ondansetron (n = 667), CYP2D6 and oxycodone (n = 99), G6PD and G6PD high-risk medications (n = 51), and CYP2C19 and proton pump inhibitors (omeprazole and pantoprazole; n = 50). The high adherence rate was facilitated by our team approach to prescribing and our collaborative CDS design and delivery.

Keywords: clinical decision support; medication alert systems; pharmacogenetics; pharmacogenomics; precision medicine.

Implementation-effectiveness trial of systematic family health history based risk assessment and impact on clinical disease prevention and surveillance activities

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R Ryanne Wu, Rachel A Myers, Joan Neuner, Catherine McCarty, Irina V Haller, Melissa Harry, Kimberly G Fulda, David Dimmock, Tejinder Rakhra-Burris, Adam Buchanan, Geoffrey S Ginsburg, Lori A Orlando
Background: Systematically assessing disease risk can improve population health by identifying those eligible for enhanced prevention/screening strategies. This study aims to determine the clinical impact of a systematic risk assessment in diverse primary care populations.
Keywords: Clinical decision support; Family health history; Health belief model; Hybrid implementation-effectiveness; Precision medicine; Risk assessment.