Photochemical Stabilization of Self-Assembled Spherical Nucleic Acids.

Oligonucleotide therapeutics, including antisense oligonucleotides and small interfering RNA, offer promising avenues for modulating the expression of disease-associated proteins. However, challenges such as nuclease degradation, poor cellular uptake, and unspecific targeting hinder their application. To overcome these obstacles, spherical nucleic acids have emerged as versatile tools for nucleic acid delivery in biomedical applications.

Chemical engineering of CRISPR-Cas systems for therapeutic application.

Clustered regularly interspaced short palindromic repeats (CRISPR) technology has transformed molecular biology and the future of gene-targeted therapeutics. CRISPR systems comprise a CRISPR-associated (Cas) endonuclease and a guide RNA (gRNA) that can be programmed to guide sequence-specific binding, cleavage, or modification of complementary DNA or RNA. However, the application of CRISPR-based therapeutics is challenged by factors such as molecular size, prokaryotic or phage origins, and an essential gRNA cofactor requirement, which impact efficacy, delivery and safety.

Canada's contributions to RNA research: past, present, and future perspectives.

The field of RNA research has provided profound insights into the basic mechanisms modulating the function and adaption of biological systems. RNA has also been at the center stage in the development of transformative biotechnological and medical applications, perhaps most notably was the advent of mRNA vaccines that were critical in helping humanity through the Covid-19 pandemic. Unbeknownst to many, Canada boasts a diverse community of RNA scientists, spanning multiple disciplines and locations, whose cutting-edge research has established a rich track record of contributions across various aspects of RNA science over many decades.

Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.

Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1.

Synthesis of Seven-Membered Ring Nucleosides and Serendipitous Simmons-Smith -Glycosylation.

A series of seven-membered (oxepine) nucleosides containing various nucleobases (A, U, T, 5-FU, C) were synthesized by ring expansion of cyclopropanated glucals. We expect this new series of ring-expanded nucleic acid analogues to be useful as building blocks in the design of mixed base functional genetic systems. While exploring alternative pathways to oxepine nucleoside synthesis, we discovered an unprecedented α-stereoselective -glycosylation of 1,2-glucals under mild Simmons-Smith conditions.