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In this article Drug Target Review’s Izzy Wood spoke to Sam Hasson, Director of Target Biology at Rgenta Therapeutics, a biotech firm in Massachusetts, US, that aims to develop smallmolecule therapeutics to target RNA processing.
Durham, North Carolina-based Ribometrix announced a strategic collaboration deal with Genentech , a Roche company, to identify and advance novel RNA-targeted smallmolecule therapeutics. Targeting RNA is believed to be a way to develop therapeutics for so-called undruggable proteins.
These tough nuts to crack in medical science—biological targets known to play roles in diseases but resistant to traditional drug design—are now seeing new strategies that shift the paradigm from "undruggable" to "druggable." Beyond Proteins: DNA and RNA Frontier The story doesn’t end with proteins.
Using what they learned from these experiments, they developed a framework — ligation-enabled messenger RNA-oligonucleotide assembly, or LEGO — that enables researchers to chemically modify the structure of mRNA molecules and influence their interactions with the cell's protein-translation machinery, achieving desired therapeutic effects.
The majority of smallmolecule drugs induce their therapeutic effects by seeking out and binding to their intended target while avoiding most other molecules in the dense milieu of the cell interior. Our overall mission at Arrakis is to expand the set of “druggable” targets for small-molecule medicines to include RNA.
Haemoglobin A1c (HbA1c) is a validated surrogate endpoint for the reduction of microvascular complications associated with diabetes mellitus; reduced HIV-RNA levels serve as an endpoint for HIV disease control; and a reduction in low-density lipoprotein (LDL) cholesterol is used as an endpoint indicating lower likelihood of cardiovascular events.
This method was more about serendipity than science. Today, we're able to identify and target specific molecules involved in disease processes—a method that's much more like using a sniper rifle than throwing darts blindfolded. But as molecular biology has advanced, so too has our approach to finding new drugs.
I studied Natural Sciences at the University of Cambridge, where I was exposed to a range of disciplines from chemistry to physiology, specialising in my last year in biochemistry. Pushing the boundaries of science always opens the door to new, impactful developments, although there are always challenges along the way.
We are moving rapidly toward escape velocity in our RNA expedition at Arrakis. For those of you joining us for the first time, it’s worth a quick look back at why we decided to go all-in on the RNA world, why people thought we were crazy, and why we know we’re not. Our terra firma is small-molecule medicines.
Since our company’s founding in 2015, we have taken the long view and been singularly focused on building an extremely flexible and broadly applicable platform that can develop a host of RNA‑targeted smallmolecules (rSMs) to deliver precision medicines for dozens of targets that have been out of reach for conventional approaches.
Smallmolecule GLP1s? Smallmolecules are still in vogue despite IRA headwinds: We continue to hear optimism for the convenience of orals even in indications with high-commercial potential and enriched for CMS coverage (likely to fall in crosshairs of IRA).
Applying our technology has enabled us to develop a new smallmolecule, TT125-802, and to assign a new role to the epigenetic regulator CBP/p300 as a novel master regulator of non-oncogene resistance. This orally available smallmolecule binds to the bromodomain of CBP/p300 in a highly specific manner.
This was a great gig – good people, good science. However, in June I happened to attend the Gordon Research Conference on Chemical Biology and High-throughput Chemistry where I saw a session on smallmolecules and RNA. Raj Parekh, a partner at Advent Life Sciences, had been thinking about this problem for a year or so.
As soon as I learned about DNA and RNA, I wanted to be a molecular biologist. Last stops at RNA My last roles in biotech were where my original passion began: DNA and RNA. My last stop at Arrakis Therapeutics is with a company targeting RNA with smallmolecules. Arrakis is the capstone of my career.
Or should I say back to retirement, as he was comfortably relaxing at home back in 2016 when Jen Petter lured him back into the fray with the siren call of developing a new class of RNA-targeted small-molecule medicines here at Arrakis. I won’t dwell on Jim’s many accomplishments here. Don’t be a stranger!
Our skilled protein science team can provide in-house production of proteins to support all these assay formats if needed. Microscale Thermophoresis (MST) Microscale Thermophoresis (MST) is a technology that uses fluorescently labelled proteins to analyse smallmolecule binding in solution.
” The report accompanies an article in Science , also released today, entitled “Confronting Risks of Mirror Life.” For the article in Science , more than 30 scientists from ten countries are calling on the broader community to confront the risks of mirrored life. ” But what, exactly, is a mirrored organism?
AT-527 is expected to be ideally suited to combat COVID-19 as it inhibits viral replication by interfering with viral RNA polymerase, a key component in the replication machinery of RNA viruses. Importantly, the manufacturing process for our smallmolecule direct-acting antiviral allows us to produce AT-527 quickly and at scale.”.
Basic Science A trailing ribosome speeds up RNA polymerase at the expense of transcript fidelity via force and allostery. Marine biofilm engineered to produce current in response to smallmolecules. Science Advances. Science Advances. Assembly of metabolons in yeast using Cas6-mediated RNA scaffolding.
Susannah is being treated with an Antisense Oligonucleotide (ASO) : To break down the term, this is a molecule designed with a sequence of 20 (oligo, “few”) letters of DNA (nucleotide) that match a sequence on the mutant KIF1A RNA (Antisense) and knock it down. With gratitude, in the Year of Pioneers.
Most people, and in particular most investors we spoke to in those early days, thought we were nuts – that RNA lacked the structural and molecular complexity that medicinal chemistry exploits with such great effect for proteins. One is that molecular recognition is purely a matter of physics and RNA has to play by the same rules.
About AstraZeneca AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology.
LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. About AstraZeneca.
Basic Science *No evidence for a common blood microbiome based on a population study of 9,770 healthy humans. Read A new DNA polymerase variant, called RT-KTq I614Y, can directly detect RNA modifications, including pseudouridine (Ψ) and queuosine (Q). Massively parallel profiling of RNA-targeting CRISPR-Cas13d.
She has played a key role inbuilding the target identification platform and a proprietary database of transcriptome-wide, functional RNA structures. Rising from Research Scientist to Senior Scientist, I supported early-stage DD efforts within their Protein Science group, based in Cambridge, UK.
The researchers first compared the editing efficiency of different versions of IscB when coupled with 'ωRNA,' which guides the enzyme to the right spot on the DNA. A particular variant, named IscB*-ωRNA*, had the highest editing efficiency across multiple different sites in the genome. Science Advances.
The researchers first compared the editing efficiency of different versions of IscB when coupled with 'ωRNA,' which guides the enzyme to the right spot on the DNA. A particular variant, named IscB*-ωRNA*, had the highest editing efficiency across multiple different sites in the genome. Science Advances.
Published in the Proceedings of the National Academy of Sciences , a new discovery from the University of Southern California (USC) on cancer metastasis has opened up new possibilities for combating the spread of this devastating disease.
Five Promising Treatment Areas in Early-Phase Drug Development in 2024 aasimakopoulos Wed, 04/17/2024 - 15:52 Early-phase drug development is an ever-changing landscape, as emerging science leads to new promising areas of research for the treatment of human health issues.
Immunization of non-human primates (rhesus macaques) with BNT162b2, a nucleoside-modified messenger RNA (modRNA) candidate that expresses the SARS-CoV-2 spike glycoprotein, resulted in strong anti-viral effects against an infectious SARS-CoV-2 challenge. billion doses by the end of 2021.
“I’m still involved with the science that we created and continue to advance,” he told BioSpace. As Crooke explained, “With smallmolecules, if you make any chemical change, you have a new ballgame. That’s not the case with RNA-targeted drugs.
Their solution was to fuse hairpins, little loops made from RNA or DNA, at various positions along the DNA strand that was being sequenced. Now equipped with more serviceable proteins and clever methods to slow down DNA traffic, nanopores could finally evolve from a niche science project to an industrial sequencing workhorse.
The Druggable Genome The Druggable Genome is the subset of all human genes encoding proteins that could be targeted with a smallmolecule or antibody drug [4]. We then designed our own CRISPR guide RNA library against the druggable genome and transduced the corresponding lentiviruses into millions of our iNeurons.
Read more at Science. Science abstracts were pulled from five different medical journals and then fed into ChatGPT. Read Ribosomes are able to build proteins because they contain a strand of RNA that imbues them with their catalytic power. Science Advances. Ann Gibbons for Science. Zhou et al. Cell Systems.
Read more at Science. Science abstracts were pulled from five different medical journals and then fed into ChatGPT. Read Ribosomes are able to build proteins because they contain a strand of RNA that imbues them with their catalytic power. Science Advances. Ann Gibbons for Science. Zhou et al. Cell Systems.
Link Basic Science *Genomic analyses of hair from Ludwig van Beethoven. Link Experimental Tests of the Virtual Circular Genome Model for Nonenzymatic RNA Replication. Link Single-molecule visualization of stalled replication-fork rescue by the Escherichia coli Rep helicase. Science Advances. Science Advances.
Experiments performed with the bacterium Streptococcus pneumoniae not only led to the discovery of DNA as the principal hereditary molecule but also yielded early tools for genetic engineering. The study of RNA tumor viruses revealed reverse transcriptase , an enzyme integral in studying RNA biology.
Strategic approach to precision medicine With an extensive background in neuroscience, Elwood oversees the science and strategy behind J&Js neurodegeneration pipeline. Her role ensures that J&Js work is at the forefront of the field, driven by robust science and strategic precision.
Read Basic Science *Noncoding translation mitigation. Science Advances. Read Open science and data sharing in cognitive neuroscience with MouseBytes and MouseBytes+. Read An RNA-based system to study hepatitis B virus replication and evaluate antivirals. Science Advances. Science Translational Medicine.
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