Research to understand RNA splicing mechanisms will facilitate drug development for genetic diseases
Cold Spring Harbor, NY — Professor Adrian Krainer of Cold Spring Harbor Laboratory (CSHL) has been selected by the National Institute of General Medical Sciences (NIGMS) to receive a MERIT (Method to Extend Research in Time) Award. This prestigious award recognizes highly productive scientists by extending funding for an existing research project grant.
Krainer is a leader in the field of RNA splicing, which has significant implications for many human genetic diseases because a high proportion of disease-causing mutations affect messenger RNA (mRNA) splicing and stability. mRNAs are the coded instructions copied from the genetic material that direct cells to manufacture specific proteins.
“NIGMS selected Dr. Krainer for a MERIT Award in recognition of his sustained record of significant accomplishments in the field of RNA splicing,” said Michael Bender, Ph.D., Program Director in the Division of Genetics and Developmental Biology, who manages Krainer’s NIGMS grant. “His work has had a major impact on our understanding of this central biological process, and it also has the potential to lead to treatments for splicing-related disorders.”
According to Krainer, his current research “will result in a better understanding of which mutations cause defective gene expression, and precisely how they do so. Thanks to support from NIGMS, we expect these findings to facilitate the development of targeted therapeutics to correct certain gene-expression defects.”
Under the MERIT Award program, Krainer’s research was selected from the pool of all current fiscal-year competing R01 grants across the National Institututes of Health. At any given time, NIGMS supports more than 4700 grants and awards five to 12 new MERIT investigators annually.
“I congratulate Dr. Krainer on this award, which recognizes the invaluable contributions that he and his lab at CSHL have made to our understanding of splicing and how it can be manipulated to overcome genetic diseases,” said CSHL President Bruce Stillman. “The MERIT Award is a clear endorsement of Dr. Krainer’s research. This vote of confidence from the National Institute of General Medical Sciences for innovative basic biomedical research is one of the necessary investments the NIH makes in the well-being our nation’s citizens.”
About Krainer’s research project
The central goal of the supported project [NIH Grant # 2 R37 GM042699-22] is to understand fundamental mechanisms of human pre-mRNA splicing, a required step in the expression of most eukaryotic genes, as well as the regulation of this process. The project relies on integrative approaches, including biochemical, molecular, proteomics, and bioinformatics techniques, as well as both cell-based and in vitro assays. In addition to obtaining new insights into basic mechanisms of gene expression, these studies will improve the understanding of numerous mutations associated with various genetic diseases, and facilitate correct genetic diagnosis and the development of therapeutics for such diseases.
Krainer’s studies funded by NIGMS have already led to the mechanism-based design of antisense compounds to correct splicing defects in target genes. The first such compound, ISIS-SMNRx, developed in close collaboration with Ionis Pharmaceuticals, entered Phase I clinical trials in November 2011. The candidate drug efficiently corrects defective splicing of SMN2 in preclinical models, and is now being tested in pediatric patients with spinal muscular atrophy (SMA), a severe motor-neuron disease for which no treatment currently exists. It is anticipated that a similar strategy can be applied for other splicing-related diseases.
About the NIH MERIT Award
The objective of the MERIT Award is to provide long-term, stable support to investigators whose research competence and productivity are distinctly superior and who are likely to continue to perform in an outstanding manner. Support to such investigators is expected to foster their continued creativity and spare them the administrative burdens associated with preparation and submission of full-length research grant applications. This may allow investigators the opportunity to take greater risks, be more adventurous in their lines of inquiry, or take the time to develop new techniques. After an initial five years of support, the MERIT awardee may request an extension of three to five years based on an eight-page progress report and a one-page abstract of the research plan for the extension period.
Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. The Meetings & Courses Program annually hosts more than 12,000 scientists. The Laboratory’s education arm also includes an academic publishing house, a graduate school and the DNA Learning Center with programs for middle and high school students and teachers. For more information, visit www.cshl.edu