Design and Delivery of SINEUP: A New Modular Tool to Increase Protein Translation

Arnoldi M, Zarantonello G, Espinoza S, Gustincich S, Di Leva F, Biagioli M.; Methods Mol Biol. 2022;2434:63-87. doi: 10.1007/978-1-0716-2010-6_4. 

Synthetic SINEUP is thus a novel molecular tool that potentially may be used for any industrial or biomedical application to enhance protein production, also as possible therapeutic strategy in haploinsufficiency-driven disorders.Here, we describe a detailed protocol to (1) design a specific BD directed to a gene of interest and (2) assemble and clone it with the ED to obtain a functional SINEUP molecule. Then, we provide guidelines to efficiently deliver SINEUP into mammalian cells and evaluate its ability to effectively upregulate target protein translation.

Recurrent repeat expansions in human cancer genomes

Erwin, G.S., Gürsoy, G., Al-Abri, R. et al.; Nature (2022). doi:10.1038/s41586-022-05515-1 

Expansions of tandem DNA repeats (TRs) are known to cause more than 50 devastating human diseases, including Huntington’s disease and fragile X syndrome1,2. TR tracts that cause human disease are typically large (more than 100 bp)1. However, identifying large TRs with short-read DNA sequencing methods is difficult because the repeat sequences are ubiquitous in the genome and many are too large—larger than the typical sequencing read length—to uniquely map to the reference genome9. Thus, many large TRs go undetected with current genomic technologies, and, despite their importance to monogenic disease, the frequency and function of recurrent repeat expansions (rREs) are unknown in complex human genetic diseases such as cancer.

Researchers may have found a new path for halting cancer cell production

Stanford Medicine; December 14, 2022; 

The project began not with cancer, but with a rare, neurodegenerative disease without a cure, Friedreich ataxia. Five years ago, Erwin, then a graduate student at the University of Wisconsin-Madison, was exploring the genetic underpinnings of Friedreich ataxia in hopes of filling the therapeutic void. Erwin knew that DNA mutations called repeat expansions cause Friedreich ataxia, along with dozens of other serious conditions, many neurological. 

Repeat expansions are stretches of DNA that erroneously repeat themselves dozens to thousands of times in the genome. 

 Testing the molecule in cells from a Friedreich ataxia patient, Erwin saw that Syn-TEF1 successfully targeted the repeat expansion, helping RNA polymerase move through it to transcribe the FXN gene, bringing frataxin to normal levels. Due to its success in cells, researchers are now testing the safety and dosage of a version of Syn-TEF1 in Friedreich ataxia patients.