Tag Archives: livestock

Effective treatment for acne sufferers with narasin encapsulated in soft nanoparticles

A September 14, 2023 news item on Nanowerk announces research that could lead to a treatment for people who suffer from acne,

It’s a skin disorder that makes life miserable for around 800 million teenagers and adults worldwide, but Australian scientists may have found an effective treatment for acne, delivered via tiny nanoparticles.

In a study led by the University of South Australia (UniSA), a new antibacterial compound known as Narasin was encased in tiny, soft nanoparticles 1000 times smaller than a single strand of human hair and applied in a gel form to targeted acne sites.

A September 14, 2023 University of South Australia press release (also on EurekAlert but published on September 13, 2023), which originated the news item, explains that narasin has been used for other purposes in the past, Note: Links have been removed,

The drug – more commonly used in the livestock industry – proved successful against drug-resistant acne bacteria and delivered via nanocarriers achieved a 100-fold increase in absorption than simply taken with water.

The findings have been published in the journal Nanoscale.

Lead author UniSA PhD student Fatima Abid says this is the first time that nano-micelle formulations of Narasin have been developed and trialled.

“Acne severely impacts approximately 9.4% of the world’s population, mainly adolescents, and causes distress, embarrassment, anxiety, low self-confidence and social isolation among sufferers,” Abid says.

“Although there are many oral medications prescribed for acne, they have a range of detrimental side effects, and many are poorly water soluble, which is why most patients and clinicians prefer topical treatments.”

Abid’s supervisor, pharmaceutical scientist Professor Sanjay Garg, says a combination of increasing antibiotic resistance and the ineffectiveness of many topical drugs to penetrate hair follicles in acne sites means there is a pressing need to develop new antibacterial therapies that are effective and safe.

Narasin is commonly used for bacterial infections in livestock but has never been previously investigated as a viable treatment for acne.

Abid, Prof Garg and researchers from UniSA, the University of Adelaide, and Aix-Marseille Université in France also investigated how well Narasin encased in nanoparticles penetrated various layers of skin, using pig’s ear skin as a model.

“The micelle formulation was effective in delivering Narasin to acne targets sites, as opposed to the compound solution which failed to permeate through skin layers,” Prof Garg says.

Here’s a link to and a citation for the paper,

Nanotechnology and narasin: a powerful combination against acne by Fatima Abid, Bhumika Savaliya, Ankit Parikh, Sangseo Kim, Marzieh Amirmostofian, Laura Cesari, Yunmei Song, Stephen W. Page, Darren J. Trott and Sanjay Garg. Nanoscale, 2023,15, 13728-13739 First published 14 Aug 2023

This paper is behind a paywall.

CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now

I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.

It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,

After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).

According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.

Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),

It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.

The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.

Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.

But the fight for patent rights to CRISPR technology is by no means over. Here are four reasons why.

1. Berkeley can appeal the ruling

2. European patents are still up for grabs

3. Other parties are also claiming patent rights on CRISPR–Cas9

4. CRISPR technology is moving beyond what the patents cover

As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.

Once you’ve read Distor’s and Ledford’s articles, you may want to check out Adam Rogers’ and Eric Niiler’s Feb. 16, 2017 CRISPR patent article for Wired,

The fight over who owns the most promising technique for editing genes—cutting and pasting the stuff of life to cure disease and advance scientific knowledge—has been a rough one. A team on the West Coast, at UC Berkeley, filed patents on the method, Crispr-Cas9; a team on the East Coast, based at MIT and the Broad Institute, filed their own patents in 2014 after Berkeley’s, but got them granted first. The Berkeley group contended that this constituted “interference,” and that Berkeley deserved the patent.

At stake: millions, maybe billions of dollars in biotech money and licensing fees, the future of medicine, the future of bioscience. Not nothing. Who will benefit depends on who owns the patents.

On Wednesday [Feb. 15, 2017], the US Patent Trial and Appeal Board kind of, sort of, almost began to answer that question. Berkeley will get the patent for using the system called Crispr-Cas9 in any living cell, from bacteria to blue whales. Broad/MIT gets the patent in eukaryotic cells, which is to say, plants and animals.

It’s … confusing. “The patent that the Broad received is for the use of Crispr gene-editing technology in eukaryotic cells. The patent for the University of California is for all cells,” says Jennifer Doudna, the UC geneticist and co-founder of Caribou Biosciences who co-invented Crispr, on a conference call. Her metaphor: “They have a patent on green tennis balls; we have a patent for all tennis balls.”

Observers didn’t quite buy that topspin. If Caribou is playing tennis, it’s looking like Broad/MIT is Serena Williams.

“UC does not necessarily lose everything, but they’re no doubt spinning the story,” says Robert Cook-Deegan, an expert in genetic policy at Arizona State University’s School for the Future of Innovation in Society. “UC’s claims to eukaryotic uses of Crispr-Cas9 will not be granted in the form they sought. That’s a big deal, and UC was the big loser.”

UC officials said Wednesday [Feb. 15, 2017] that they are studying the 51-page decision and considering whether to appeal. That leaves members of the biotechnology sector wondering who they will have to pay to use Crispr as part of a business—and scientists hoping the outcome won’t somehow keep them from continuing their research.

….

Happy reading!

Alberta’s Domino (point-of-care diagnostic) and Navacim (nano drug delivery) competing for $175,000 prize

It’s interesting that two nanomedicine products are in contention for TEC Edmonton‘s NanoVenture Prize. It’s a new prize category for the business accelerator in this, their 10th anniversary year. From TEC Edmonton’s March 27, 2012 news release,

The NanoVenturePrize finalists are Aquila Diagnostics of Edmonton and Calgary’s Parvus Therapeutics.

Aquila Diagnostics uses the Domino nanotechnology platform developed at the University of Alberta to provide on-site, easy-to-use genetic testing that can quickly test for infectious diseases and pathogens in livestock. The mobile diagnostic platform is portable, low-cost, fast and easy to use.

Parvus Therapeutics’ breakthrough nanomedicines may hold the cure for difficult-to-treat autoimmune diseases like type 1 diabetes, multiple sclerosis and inflammatory bowel disease. Parvus’ new Navacim medicines are nanoparticles coated with immune system proteins that can target specific autoimmune conditions.

The University of Alberta has issued its own April 24, 2012 news release by Bryan Alary about the Domino,

Dubbed the Domino, the technology—developed by a U of A research team—has the potential to revolutionize point-of-care medicine. The innovation has also earned Aquila Diagnostic Systems, the Edmonton-based nano startup that licensed the technology, a shot at $175,000 as a finalist for the TEC NanoVenturePrize award.

“We’re basically replacing millions of dollars of equipment that would be in a conventional, consolidated lab with something that costs pennies to produce and is field portable so you can take it where needed. That’s where this technology shines,” said Jason Acker, an associate professor of laboratory medicine and pathology at the U of A and chief technology officer with Aquila.

The Domino employs polymerase chain reaction technology used to amplify and detect targeted sequences of DNA, but in a miniaturized form that fits on a plastic chip the size of two postage stamps. The chip contains 20 gel posts—each the size of a pinhead—capable of identifying sequences of DNA with a single drop of blood.

Each post performs its own genetic test, meaning you can not only find out whether you have malaria, but also determine the type of malaria and whether your DNA makes you resistant to certain antimalarial drugs. It takes less than an hour to process one chip, making it possible to screen large populations in a short time.

“That’s the real value proposition—being able to do multiple tests at the same time,” Acker said, adding that the Domino has been used in several recently published studies, showing similar accuracy to centralized labs.

Linda Pilarski, an oncology professor at the University of Alberta (mentioned in my Jan. 4, 2012 posting about her diagnostics-on-a-chip work), and her team developed Domino according to the April 25, 2012 news item on Nanowerk,

In 2008, her team received $5 million over five years from Alberta Innovates Health Solutions to perfect and commercialize the technology. As an oncologist, Pilarski is interested in its pharmacogenomic testing capabilities, such as determining whether breast cancer patients are genetically disposed to resist certain drugs.

“With most cancers you want to treat the patient with the most effective therapeutic as possible,” she said. “That’s what this does: it really enables personalized medicine. It will be able to test every patient at the right time, right in their doctor’s office. That’s currently not feasible because it’s too expensive.”

This product is intended for the market but not the one you might expect (from the April 25, 2012 news item on Nanowerk),

Along with its versatility, two key selling points are affordability and portability, with each portable box expected to cost about $5,000 and each chip a few dollars, says Aquila president David Alton. It’s also designed to be easy to use and rugged—important features for the livestock industry, the company’s first target market. [emphasis mine] The Domino will be put through trials within a year at one of the country’s largest feedlots in southern Alberta.

Alton credits Aquila’s relationship with the U of A, not just for the research but for the business relationship with TEC Edmonton that has helped the company license and patent Domino. TEC Edmonton is a joint venture between the U of A and Edmonton Economic Development Corporation with resources and expertise to help startups in the early stages of operations.

“We see a huge potential market for the technology and we’re looking at applying the technology developed here at the U of A to markets first in Alberta and then globally, to address important health issues here and throughout the world.”

Given that the originator is an oncologist I really wasn’t expecting the first market to be livestock industry.

I have had a little less luck getting information about Parvus Therapeutics’ Navacim technology as they’ve not issued a news release about their competition for this prize but I did find some information on their website, from an April 8, 2010 news release about the Navacim technology being featured in a Popular Science article,

Parvus Therapeutics reports that an article entitled “Nanotech Vaccine Successfully Cures Type-1 Diabetes in Mice” has been published at the website of Popular Science. The article, authored by Alessandra Calderin, describes the Parvus Navacim technology and includes remarks from Parvus’ Founder and Chief Scientific Officer, Dr. Pere Santamaria.

The article notes that,

“The technology behind the nanovaccine, following further research, may prove widely applicable to treat other autoimmune diseases, like arthritis and multiple sclerosis, as well.”

You may want to take a look at the news brief by Calderin. Here’s more about the technology, from the Introducing Navacims webpage on the Parvus Therapeutics website,

Our nanotechnology-based therapeutic platform and Navacims, the therapeutic candidates, are the result of two related discoveries: A new class of immune cell, and a new way to treat autoimmunity that these cells provide. Here we provide a very brief summary of how these discoveries came about and what they have led to since.

This summary is also intended as a roadmap to the contents of this technology section of our website, which we will role out over a period of weeks and adapt based on reader feedback and requests. The casual reader may find the background information helpful, while our professional colleagues will probably want to get straight down to the technical details and published papers. We have tried to design the content to cater to all tastes and it can be read in any order, although like all good stories, we highly recommend starting at the beginning.

As with the remainder of our site, we have injected a little colour and a little humour to keep your spirits up if the science appears a little daunting. In all, we have attempted to strike a balance between scientific detail and general accessibility and if you think we have that balance wrong, or you feel something is missing, please let us know — via the form on the Contacts page — and we will try to put it right. We love to hear from you.

The Story So Far

[1] In a series of experiments, only tangentially related to our current activities, we designed p-MHC-coated nanoparticles (NPs) as a way to load iron into effector T-cells and have them ferry the iron to the pancreas so we could visualize pancreatic islet cell inflammation in-vivo, in real-time — this amounts to the use of a Magnetic Resonance Imaging (MRI) contrast agent.

[2] It occurred to us that we might be able to use these p-MHC-NPs to delete the high avidity cytotoxic effector T cells driving disease in the NOD mouse model of type 1 diabetes (T1D).

[3] Too our surprise, therapy did not delete, but rather, very significantly expanded autoregulatory T cell pools.

[4] After careful analysis we were able to conclude that:

pMHC-NPs, now called Navacims, selectively expand a population of low avidity autoregulatory memory T cells that the disease itself generates — this population of cells was previously unknown to science. These cells target and kill antigen presenting cells (APCs), and consequently, interput the process whereby all the cytotoxic effector T cell lineages active in a disease are activated and expanded.

Navacims also directly deplete the high avidity cytotoxic effector T cells cognate to the pMHC carried by the nanoparticle. This removes one lineage of cells that cause damage in disease, but given the many antigens, and consequently the many T cell lineages, the overall therapeutic effect of removing one type is inconsequential compared to the indirect effect of the Navacim on APCs that removes all lineages.

The removal of APCs and the concomitant loss of multiple cytotoxic effector T-cell lineages that drive disease amounted to a cure for T1D in the NOD mouse model.

[5] We believe that Navacims have the potential to become the long sought after ideal treatment for autoimmunity; a therapeutic that restores immunological tolerance — the principal problem in autoimmunity — while depleting autoreactive cells that mediate the damaging effects of disease.

[6] Navacims appear to be safe and very well tolerated in animal experiments that have lasted many months, although we caution that we have yet to complete formal toxicological studies.

[7] Navacims are highly modular and a family of Navacims can be almost identical, differing only in the very short antigenic peptide that gives each one its specificity for a particular disease.

[8] Because they are so similar, we beleive that industry-standard manufacturing processes will need few if any modifications in order to produce a particular Navacim.

[9] We have protected our discoveries with patent applications in the United States, Europe, Canada, and beyond.

[10] Our work has been published in top-ranked peer-reviewed journals and showcased in the best of the popular science publications.

Good luck to both companies in their future endeavours.

ETA April 30,2012: According to the April 27, 2012 article in the Edmonton Journal, Parvus Therapeutics won the $175, 000 prize in TEC Edmonton’s new prize category.,

This year’s awards, the 10th consecutive, added a new category for nanotechnology firms. TEC partnered with Alberta Innovates — Technology Futures for the new award. Calgary’s Parvus Therapeutics, which makes medicine aimed at autoimmune diseases such as Type 1 diabetes and multiple sclerosis, beat out Edmonton’s Aquila Diagnostic Systems for first place. The category’s prizes totalled $175,000 in cash and services.