Selecting a Cell Engineering Methodology During Cell Therapy Product Development.

When considering the development pathway for a genetically modified cell therapy product, it is critically important that the product is engineered consistent with its intended human use. For scientists looking to develop and commercialize a new technology, the decision to select a genetic modification method depends on several practical considerations. Whichever path is chosen, the developer must understand the key risks and potential mitigations of the cell engineering approach.

Role of PI3K/Akt signaling in TRAIL- and radiation-induced gastrointestinal apoptosis.

Activation of the PI3K/Akt pathway is associated with tumorigenesis and resistance to apoptosis and ionizing radiation (IR). We sought to characterize the effects of physiologic and genetic manipulation of Akt signaling on IR-induced gastrointestinal (GI) apoptosis in mice. PI3K/Akt signaling is stimulated by insulin.

Interaction of yeast RNA-binding proteins Nrd1 and Nab3 with RNA polymerase II terminator elements.

Yeast RNA-binding proteins Nrd1 and Nab3 direct transcription termination of sn/snoRNA transcripts, some mRNA transcripts, and a class of intergenic and anti-sense transcripts. Recognition of Nrd1- and Nab3-binding sites is a critical first step in the termination and subsequent processing or degradation of these transcripts. In this article, we describe the purification and characterization of an Nrd1-Nab3 heterodimer.

Regulation of yeast NRD1 expression by premature transcription termination.

The yeast RNA binding proteins Nrd1 and Nab3 are required for termination of nonpolyadenylated transcripts from RNA polymerase (Pol) II-transcribed snRNA and snoRNA genes. In this paper, we show that NRD1 expression is regulated by Nrd1- and Nab3-directed premature termination. Sequences recognized by these proteins are present in NRD1 mRNA and are required for regulated expression.

Identification of cis elements directing termination of yeast nonpolyadenylated snoRNA transcripts.

RNA polymerase II (Pol II) termination is triggered by sequences present in the nascent transcript. Termination of pre-mRNA transcription is coupled to recognition of cis-acting sequences that direct cleavage and polyadenylation of the pre-mRNA. Termination of nonpolyadenylated [non-poly(A)] Pol II transcripts in Saccharomyces cerevisiae requires the RNA-binding proteins Nrd1 and Nab3.