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Gut Check: using transfection to study the gut microbiome’s role in inflammation

Today’s SNiP reminds us that we are never truly alone. It’s been estimated that over one trillion microbial cells inhabit the human body. In this study, Wojciech et al. implicate a eukaryotic gut-dwelling microbe, Blastocystis subtype 7, in host T cell dysregulation, providing a mechanism for how this microbe can cause inflammation in the gut.

Tune-In to the Immune System with Label IT®

Today’s TransMission explores an unconventional application of Mirus Bio’s Label IT® Nucleic Acid Labeling kits in engineering a new method of vaccine delivery, the microneedle array (MNA). MNAs are patches of micron-scale needles that delicately penetrate the skin in a painless manner, accessing an immune-rich population of cells. In this study, the authors fluorescently labeled immune-stimulating oligos using Label IT® Cy®3 and Label IT® Cy®5 to visualize their distribution on MNAs.

Read on to learn more about this unique method of stimulation!

Mixed Messages: a SNiP Double Feature

Cartoon of model organisms playing telephone with mRNA.

Transfection of three-dimensional cellular structures, like tissues and organs, and whole organisms can be tricky to accomplish. Today’s TransMission highlights not one but two SNiPs of studies featuring mRNA delivery to live planarian worms and rat fetuses. Read on to learn the methods employed by the authors of these studies to achieve this formidable feat!

Enrich CRISPR’d Cells with Label IT®

Icon showing cells sorted with Label IT and Cas9 RNP.

Today’s TransMission is a SNiP of one of our favorite papers featuring Label IT®. Nasri and Mir et al. describe an elegant use for Label IT® in enriching CRISPR/Cas-edited cells. For use in the clinic, it is highly desirable to limit the number of nonedited cells that may compete with the therapeutic, modified cells. Read on to learn how Label IT® was used to enhance the CRISPR genome-editing workflow!

Crossing the BBB with Nanobodies

Diagram of a nanobody with knob-into-hole feature binding BACE1.

The blood brain barrier (BBB) protects our brains from circulating pathogens and inflammatory cells. However, it also prevents the delivery of therapeutics into the brain. In this SNiP, we highlight a study from Rué et al. that describes a bispecific nanobody construct that can bind an Alzheimer’s disease target as well as a receptor at the BBB interface to promote entry into the brain.

CRISPR Prime Editors Unleashed

“United we stand, divided we… small?”

CRISPR prime editing, introduced in 2019, harnesses a Frankensteinian enzyme–a Cas nickase fused to a reverse transcriptase–to perform gene edits with putatively higher fidelity than traditional CRISPR/Cas genome editing systems. In this SNiP, we highlight recent work from Grünewald et al. that shows the prime editor fusion can be split without negative consequence to editing, suggesting that the nickase and reverse transcriptase modules operate in trans. This finding is a boon for delivery and use of prime editing machinery with space-constrained vectors, such as AAV and lentiviral vectors.

Read on to learn more about prime editing and the authors’ discovery.

Chromothripsis and the Epstein-Barr Virus

Chromothripsis is a term used to describe chromosome shattering. In this SNiP, we highlight a recent study by Li et al. that revealed a link between Epstein-Barr Virus (EBV) infection and chromosomal instability. The authors identify a locus on chromosome 11q23 that is susceptible to binding by multiple copies of the EBV protein EBNA1. They propose a mechanism by which this concentrated binding and subsequent chromosomal breakage could explain the association between EBV and a variety of cancers.

And, did we mention that >90% of adults worldwide live with EBV? Read on to learn more.

Targeting STMN2 Splicing to Treat ALS

Today’s TransMission is a SNiP (Small News in Pieces) about stathmin-2, which is encoded by the STMN2 gene. No, this is not a pun on a Jason Statham action movie. STMN2 is a potential drug target for amyotrophic lateral sclerosis (ALS). In this SNiP, we highlight how Baughn & Melamed et al. modulate splicing of STMN2 mRNA with antisense oligonucleotide- and CRISPR-based approaches. The strategies and tools introduced in their study will be useful in the development of gene therapies to treat ALS and related neurodegenerative diseases.

Hitting HIV with Combo Therapy

The field of HIV/AIDS medicine is no stranger to combination therapy. In this SNiP (Small News in Pieces), we highlight a paper from Usero et al. that suggests using an mRNA-based HIV vaccine in combination with immunomodulators to clear HIV infection.

Giving a Hand to Zinc Finger Transfection

Today’s TransMission is a SNiP (Small News in Pieces) about zinc fingers and the subtleties in zinc finger design. Zinc fingers are an alluring biotherapeutic modality because of their natural prevalence in humans, modularity, small size (~30 amino acids per finger) and DNA-targeting ability. However, zinc finger protein design remains challenging because DNA binding specificity and affinity is affected by the presence of adjacent zinc fingers in an unclear pattern.

Read today’s TransMission to learn how Ichikawa et al. applied machine learning in hopes of developing a proverbial ‘Zinc Finger Rosetta Stone’ for designing zinc fingers capable of targeting any genomic sequence.