[R01] Beginning genetic interventions in infants (BEGIN)
Ente: National Human Genome Research Institute
Scadenza: 2030-03-31
Importo max: 3.151.302 EUR
Paese: US
Descrizione
PROJECT SUMMARY
The advancements in genomic medicine have significantly accelerated over the past decade. However, their
translation into clinical practice have been slow, and the precise treatment options are essentially nonexistent.
The formulation of effective therapies is obstructed by the vast diversity of genetic diseases and the limited
number of patients diagnosed with any specific genetic condition. Furthermore, the inefficiency often
encountered in diagnostic workups leads to delayed diagnoses for children, rendering it difficult to test
interventions effectively at an appropriate stage of their condition. There exists an urgent necessity to bridge
the disparities between the prompt identification of patients who are likely to have a genetic disease, the
delineation of a precise genetic diagnosis, and the development of effective precision therapies.
This project is centered on the Neonatal Intensive Care Unit (NICU) and establishes a framework for an
innovative approach to addressing its challenges by integrating rapid turnaround diagnostics with expedited
gene-targeted therapies. Within this model, we will provide rapid genome sequencing to patients in the NICU,
where many severe childhood genetic conditions initially present—approximately 20% of all admissions—thus
offering the opportunity for early diagnosis, prior to irreversible disease progression. Furthermore, we will
leverage our VIGOR network and collaborate with comprehensive sequencing facilities, such as GeneDx, to
identify NICU cases that exhibit specific types of mutations and conditions that qualify them for patient-
customized antisense oligonucleotides (ASOs) therapies. These ASOs are modular therapeutic agents
composed of snippets of synthetic DNA or RNA, ranging from 15-30 nucleotides, which can be flexibly tailored
to modulate specific gene-splicing patterns or target genes for degradation. Our previous work has
demonstrated the feasibility of developing ASOs as a platform for precision treatment in several genetic
conditions. This proposal lays the groundwork for the implementation of precision medicine within the NICU.
We will focus on identifying opportunities to use ASOs to treat NICU infants with various rare genetic disorders
due to the pharmacological advantages conferred by ASOs. In Aim 1, we will conduct rapid genome
sequencing on a cohort of NICU infants with rare genetic conditions and implement a systematic algorithm to
identify pathogenic variants amenable to ASO intervention sourced from diverse resources. In Aim 2, we will
establish a biorepository to preserve biospecimens and assess their ASO amenability through RNA
sequencing, subsequently referring them to laboratories and non-profit organizations for the advancement of
ASO-based therapeutic modalities. In Aim 3, we will survey the families and healthcare providers regarding this
precision NICU care model. This initiative will address the pressing necessity for translational genomic
medicine for in
Istituzione: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
PI: PANKAJ B AGRAWAL, Timothy Wei-Wen Yu
Progetto: 1R01HG014337-01A1
Settori: National Human Genome Research Institute
Vai al bando originale
Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.