Judy Muller-Cohn

Following nature's lead: generating compounds for stabilizing biomolecules.

We describe here a unique approach to identifying small molecules that are useful in stabilizing biomolecules in the dry and liquid states. Using biostability screens aided by in silico docking experiments and synthetic chemistry, libraries of biostability molecules are analyzed for their ability to protect important biological materials. In the case of DNA stabilization in the dry state, interactions of suitable candidate biostability compounds with DNA are studied in initial screens to identify their ability to form glasses at elevated temperatures. The most promising compounds are then tested for their capacity to preserve DNA during long-term storage. The results have led to a commercial product for storage of DNA that is being adopted for many commercial and experimental applications. Further studies have shown that small molecules for preservation of RNA, proteins, and tissue samples can be developed by following the same progression of screens.

Abstract 5542: Gene expression and genomic DNA stabilization in whole blood stored at room temperature

Genomic and mitochondrial DNA and gene expression profiles from blood samples are increasingly being used to diagnose specific diseases, including cancer, monitor disease progression and assess patient responses to medical treatment. However, such applications require reliable preservation of total RNA and DNA in patient samples during collection, transport and storage. Numerous agents threaten DNA and RNA profiles in collected blood samples, including nucleolytic attack, oxidative damage and hydrolysis. Such damage can severely disrupt genotyping and DNA sequencing efforts. Transcription profiles are highly dynamic and can change rapidly during and after blood collection using current methods, potentially affecting interpretation of the expression analysis, and ultimately lead to inadequate treatment options. In this study, we compare freezer storage with room temperature stabilization formulations, DNAgard Blood and PAXgene Blood DNA, in their capacities to preserve genomic DNA integrity in human whole blood for 8 months. In a separate analysis, we compare freezer storage with room temperature stabilization formulations, PAXgene Blood RNA and Biomatrica formulation DRG, in their capacities to stabilize RNA in whole blood samples. We assess changes in the relative expression of a panel of 34000 genes in whole blood specimens over the course of 7 days using RT-qPCR and the Human HT-12 Bead Array (Illumina). Our results demonstrate that room temperature blood storage is a valid alternative to cold-storage for preserving gDNA for more than a year, and RNA for at least 7 days. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5542. doi:1538-7445.AM2012-5542