- Publications Citing TriLink Products Exceed 6,000
- TriLink Products Showed up at a Rate of One Publication per Work Day
- Among These Customer Publications, Modified mRNA is Trending
From my college classes decades ago, I can still clearly recall—thankfully—many “ah ha” moments. Most importantly is when I crystalized to purity and then confirmed structure by NMR the first compound I synthesized in Organic Chemistry Lab. Another ah ha moment—but on a completely different level—was during a philosophy class when the professor partially paraphrased a quote by Aristotle as “we are what we do.” The full quote given above is even more thought provoking because it ties in the notion of excellence, which I took to heart then, and have attempted to live by ever since.
The “we” and “excellence” extends not only to teams in sports but also companies. So when I was recently musing about 2016 marking TriLink’s 20th Anniversary and what it means, Aristotle’s sage opining came to mind. Then, in a quick series of mental flashes, I recognized that TriLink’s commercial longevity—and its tag line as “The Modified Nucleic Acid Experts”—reflect the excellence of the science that its customers collectively “do” and publish. That’s the genesis of this blog, which focuses on TriLink customer publications in 2015 that I’ve selected for commenting, and also some earlier customer work distinguished by being most cited. You can also click here to find out more about what TriLink has been doing over the past 20 years.
TriLink Customer Productivity in 2015
Since opening its doors for business twenty years ago, TriLink Biotechnologies grew from having its first customer to now having thousands of customers around the world at all types of colleges, universities, institutions, and companies. While there’s no way to know and peruse everything these folks investigate, their work leading to publications in which TriLink is specified as a supplier can be found through the amazing power of the internet.
Having said that, I took a “snapshot” of TriLink customer productivity (i.e. publications and patents) in 2015 by searching Google Scholar for the word “trilink,” unchecking citations, and then clicking “Since 2015.” Having performed this search in early Jan 2016, the found items totaling 266 cover a period of time just a tad over 12 months. So, if you allow me to assume 5 days per work week, the math gives very close to 1 publication or patent per day. This publication rate reflects—in my opinion—quite impressive TriLink customer productivity, especially when you also consider the additional scientific findings that are presumably published without citing TriLink as a supplier, or remain as significant but unpublished results (e.g. clinical diagnostics or commercial trade secrets).
Selected TriLink Customer Publications in 2015
Frankly, I was amazed by the scope and diversity of scientific publications among the aforementioned 266 found items, and deciding which to select for commenting here was neither easy nor entirely objective. However, as the saying goes, “it’s a tough job, but somebody has to do it.” So after emulating—not posing as—Rodin’s The Thinker for some time, the following are my unranked picks with brief comments.
- Cell-internalization SELEX: method for identifying cell-internalizing RNA aptamers for delivering siRNAs to target cells by Thiel et al. in RNA Interference. I’ve previously commented on the growing interest in, and utility of, aptamers as ‘chemical antibodies’ that can offer significant advantages. This report describes incorporation of TriLink 2’-fluoro cytosine-5’-triphosphate (2′F-CTP) and its uracil congener (2′F-UTP) into nuclease-resistant RNA aptamers that can target cells for more efficient uptake of siRNA.
- In Vitro Evaluation of a Novel mRNA-Based Therapeutic Strategy for the Treatment of Patients Suffering from Alpha-1-Antitrypsin Deficiency by Michel et al. in Nucleic Acid Therap. In vitro transcribed modified mRNA encoding alpha-1-antitrypsin as a novel therapeutic strategy was prepared using TriLink pseudouridine-5′-triphosphate (Pseudo-UTP) and 5-methylcytidine-5′-triphosphate (Me-CTP). This is an example of the emerging field of mRNA therapeutics that I’ve previously coined here as ‘Modified mRNA Mania.” My blog archive also has two posts featuring pseudouridine per se.
- Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η by well-known crystallographer Martin Egli and coworkers in Biol. Chem. Oligonucleotides containing an abasic site or a tetrahydrofuran analog thereof were synthesized by TriLink. I was attracted to this item in view of the 2015 Nobel Prize in Chemistry for mechanistic studies of DNA repair.
- Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells by Lee et al. in J. Nanomedicine. Another instance of the increasing interest in mRNA therapeutics, this time enabled by 3′-O-Me-m 7 G(5′)ppp(5′)G RNA cap analog, Me-CTP, Pseudo-UTP, and enhanced green fluorescence protein (eGFP)—all from TriLink.
- Synthesis of 2′-Fluoro RNA by Syn5 RNA polymerase by uber-famous-for-DNA-sequencing Tabor & Richardson report in Nucleic Acids Res. that RNA polymerase from the marine cyanophage Syn5 has an intrinsic low discrimination against 2’-F-dNTPs (from TriLink) for incorporation of 2′-fluoro dNMPs during transcription elongation. The substitution of 2′-F for 2′-hydroxyl moieties in RNA substantially improves the stability of RNA, thus enabling many applications.
- Profiling Long Noncoding RNA Expression Using Custom-Designed Microarray by Zhang et al. in Volume 1402 of Methods in Molecular Biology use Cy3 Random Nonamers from TriLink for labeling for investigations of long noncoding RNA. These RNAs are now recognized as important for gene expression, and are encoded in what formerly was called “junk DNA.” See my blog archive for more on this topic.
- CTAB enhancement of FRET in DNA structures by uber-famous-for-FRET-probes-invention Michael J. Heller reports in Journal of Biophotonics more advances in FRET using dye-conjugated and non-conjugated oligonucleotides supplied by TriLink.
- A crystal structure of the dengue virus NS5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication by Zhao et al. in PLOS employs a GpppA-7mer RNA from TriLink. This publication has already been cited 15 times, which is relatively high and thus attests to its scientific impact.
- Derivation of GMP-compliant integration-free hiPSCs using modified mRNAs by Durruthy & Sebastiano in Stem Cells and Good Manufacturing Practices uses modified mRNAs encoding for OCT4, SOX2, KLF4, cMYC, LIN28A, and GFP supplied by TriLink, which has recently established its own GMP manufacturing facilities for modified mRNA and other intended pharmaceuticals related to nucleic acids.
- Genetic Control of Replication through N1-methyladenine in Human Cells by Conde et al. in Biol. Chem. identifies the translesion synthesis (TLS) DNA polymerases (Pols) required for replicating through N1-methyl adenine (1-MeA), which is formed in DNA by reaction with alkylating agents and naturally occurring methyl halides. They show that TLS through this lesion is mediated via three different pathways in which Pols ι and θ function in one pathway and Pols η and ζ, respectively, function in the other two pathways. In my opinion, this is yet another example of the wondrous complexity of macromolecular biology!
- Screening of mRNA chemical modification to maximize protein expression with reduced immunogenicity by Uchida et al. in They note that, for mRNA modification, chemically modified nucleotide triphosphates, such as 5-methyl-cytidine, 2-thio-uridine, and pseudo-uridine were supplied by TriLink.
By now you’ll have likely recognized that use of base-modified NTPs for synthesis of modified mRNA is trending among these TriLink customer publications in 2015. To underscore this conclusion, here are a few more 2015 modified mRNA publication titles:
- N 1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced …
- Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes
Hopefully this blog inspired by my Aristotelian musings has provided some illuminating information about TriLink customer publications that reflect the excellence of the products supplied. TriLink looks forward to another 20 years of providing excellence in nucleic acids products and manufacturing.
As usual, your comments are welcomed.