Posts Tagged ‘nanotechnology’

Plant-Based Vaccines, Antibodies and Biologics 5: Part 1

27 June, 2013

Plant-Based Vaccines, Antibodies and Biologics: the 5th Conference

Verona, Italy, June 2013

The return of this biennial meeting to Verona – the third time it has been held here – was a welcome change; while the previous meeting in Porto in 2011 may have been good, the city was nothing like as pleasant a place to relax.  My group is now familiar enough with Verona that we know just where to go to get pasta by the riverside – or, on this occasion, “colt loin with braised onion and potatoes” and “stewed horse with red wine”.  Which seem more palatable, somehow, as “Costata di puledro con cipolle brasate e patate” and “Stracotto di cavallo speziata” respectively, but were enjoyed anyway.

The conference kicked off with an opening plenary session, chaired by the Local Organizing Chair, Mario Pezzotti, of the University of Verona.  The headline act was a talk on taliglucerase alfa – aka glucocerebrocidase, a Gaucher Disease therapeutic  –  by Einat Almon of Protalix Therapeutics from Carmiel, Israel.  I featured the product here last year, after an earlier feature here; suffice it to say that it has soared since FDA approval, and now Protalix is pushing hard with new plant-made products to follow it up.  While they use carrot cells for taliglucerase alfa, apparently they are using suspension-cultured tobacco cells for other products – and are using an easily-scalable disposable 800 litre plastic bag system, with air-driven mixing of cells suspended in very simple, completely mammal-derived product free media.  Hundreds of patients had been treated with the drug for up to 5 years with no ill effects, and the possibility of switching therapies from mammalian cell-made products to the plant cell-made had been successfully demonstrated.

Scott Deeter of Ventria Biosciences (Ft Collins, USA) spoke next, on “Commercializing plant-based therapeutics and bioreagents”.  His company has possibly the most pragmatic attitude to the production and sale of these substances that I have yet met, and he struck a number of chords with our thinking on the subject – which of course, post-dates theirs!  Ventria use self-pollinating transgenic cereals for production of seed containing the protein of interest, and rice in particular, for safety reasons – and because the processing of the seeds is very well understood, and the purification processes and schedules are common to many food products and so do not require new technology.  He reckoned that a company starting out in the business needed an approved product in order to give customers confidence – but should also engage in contract services and contract manufacture of client-driven products in order to avoid being a one-product shop.  To this end, they had received APHIS Biological Quality Manufacturing Systems (BQMS) certification (similar to ISO9001), with the help of the US Biotechnology Regulatory Services.

Their therapeutic products included diarrhoea, ulcerative colitis and osteoporosis therapeutics which were already in phase II clinical trial.  Scott noted that in particular, recombinant lactoferrin was a novel product, which could only feasibly be produced in the volumes and at the price required for effective therapy, by recombinant plant-based production systems.  It also filled a high unmet need as a therapy for antibiotic-associated diarrhoea in the US, with +/-3 million patients at risk annually who presently cost service providers over $1500 each for treatment.

A third commercialization option was bioreagents and industrial enzymes, which they marketed via a vehicle called InVitria: they had a number of products already in the market, which Scott claimed gave confidence to the market and to partners, while building capacity to make therapeutics.  Something that was particularly attractive to our prospects was that a collection or pool of small volume products – say $5-10 million each – gave a respectable portfolio.  He noted that Sigma Aldrich and Merck were already marketing their human serum albumin, which competed effectively with serum- and yeast-derived products.

George Lomonossoff from the John Innes Centre in Norwich, UK, spoke next on “Transient expression for the rapid production of virus-like particles in plants” – a subject close to our hearts, seeing as we have for the last five years been associated with George and partners in the Framework 7-funded PlaProVa consortium.  He mentioned as an object example the recent success in both production and an efficacy trial of complete Bluetongue virus (BTV) serotype 8 VLPs, made in Nicotiana benthamiana via transient expression using their proprietary Cowpea mosaic virus (CPMV) RNA2-derived pEAQ vector: this was published recently in Plant Biotechnology Journal.

Another very useful technology was the use of CPMV capsids as engineered nanoparticles: one can make empty VLPs of CPMV at high yield by co-expressing the coat protein (CP) precursor VP60 and the viral 24K protease: the particles are structurally very similar to virions in having a 0.85 nm pore at 5-fold rotational axes of symmetry, meaning they can be loaded with (for example) Co ions.  It is also possible to fuse targeting sequences – such as the familiar RGD loop – into the surface loops of the CPMV CPs, and to modify the inner surface too.  One application would be to engineer Cys residues exposed on the inside, which could bind Fe2+ ions: this would result in particles which could be targeted to cancer cells by specific sequences, then heated using magnetic fields.

John Butler of Bayer Innovation GmbH (Leverkusen, Germany) closed out the session with an account of lessons learned from the development of the plant-derived non-Hodgkins lymphoma (NHL) vaccine, that they had acquired with Icon Genetics, who in turn had inherited it from the sadly defunct Large Scale Biology Corp.  It was rather depressing to hear that Bayer had dumped the vaccine, despite the developers having reached their targets in turning 43 of 45 tumour samples into lifetime individualized supplies of vaccine within12 weeks, and despite the phase I trial being as successful as could be hoped.  To this end, the vaccines had been well tolerated and were immunogenic; of the patients who reacted immunologically, all but one were still tumour-free presently.

He felt that the problem was that NHL trials were too long and therefore too expensive as it was a slow-progressing disease; that a different clinical approach was needed, and that using the vaccines as a first-line therapy instead of only after the 2nd or 3rd relapse would be a much better idea.  The main lesson learned was that proving the technology would be far better done with a therapeutic vaccine for a fast-acting cancer, which would allow 1-2 year clinical trials with overall survival as an endpoint.

(more coming)

Nano Patents and Innovations: Powerful New Approach To Attack Flu Virus

28 May, 2012

See on Scoop.itVirology and Bioinformatics from Virology.ca

An international research team has manufactured a new protein that can combat deadly flu epidemics.

The paper, featured on the cover of the current issue of Nature Biotechnology, demonstrates ways to use manufactured genes as antivirals, which disable key functions of the flu virus, said Tim Whitehead, assistant professor of chemical engineering and materials science at Michigan State University.

See on nanopatentsandinnovations.blogspot.fr

Viruses as nanomachines! Or: what you can believe from YouTube

6 December, 2010

I have for some years now been teaching my undergrad students that virus particles are nanomachines: that is, they are highly sophisticated nanoscale (read: ultramicroscopic) devices whose function is to specifically deliver genetic material into an environment where it can be expressed and replicated, so as to make more virus particles.

Nanoscale von Neumann machines, then – and if you want to see what a macroscale vN machine could do, just watch “2010: Odyssey Two“.

Ah, but what’s a von Neumann machine, you ask?  Well, I note Wikipedia has the following:

  • Self-replicating machines, a class of machines that can replicate themselves
  • Universal Constructors, self-replicating cellular automata
  • Von Neumann probes, hypothetical space probes capable of self-replication
  • Nanorobots capable of self-replication

I especially like the last two – because, as I showed in a previous blog post, I like the idea of virus particles or virions as “inner space craft”.  That this neatly marries my recreational and professional reading is no coincidence – because they cross-pollinate one another, in that I get ideas about the nature of viruses from SF, and my virology training informs scenarios I would like to write about.  Someday.  Soon, possibly.  Really.  Instead of writing about parallel universes contactable via the internet….

However, there is more to viruses and nanotechnology than phages with contractile tails, whether or not they have been around for billions of years: mimiviruses too have both nanoscale DNA loading and rapid-delivery systems, as previously discussed here.

Although I have a passing fondness for possibly my most successful animation – made from actual EMs, done by Linda Stannard.

T4 phage infecting a cell

So it was with some pleasure I saw recently on YouTube a video labelled “Viruses are nanotechnology (how a virus works)“.  I was a little less pleased when a voice confidently announced that “…a virus isn’t alive, people – it’s non-metabolising…”, as if that was the sole and necessary criterion for life.  I am at one with another Polish-named person – one Bernard Korzeniewski – in thinking  that life is (from MicrobiologyBytes)

The phenomenon associated with the replication of self-coding informational systems” © E.P. Rybicki, 1996. Incidentally, I find another person with a Polish name has said something very similar, in 2001 – which means it must be true. Bernard Korzeniewski describes life as: “A network of inferior negative feedbacks subordinated to a superior positive feedback.”

See, no mention of metabolism – or even of cells!  But what got the hairs on the back of my neck standing up, however, was some of the rest of it – delivered in a smooth, folksy manner, with stunning video footage.  Absolute cr@p, most of it: viruses are too complicated to have evolved, so they have to be alien nanotech???

Obviously some weird kind of conspiracy theory cross technobabble – but very seductive, to the uninformed.  Some of the comments are also just out of this world – literally!

Fortunately, there are some real science videos out there too – some of which I have also used in lecturing, if only to illustrate just how cool structural biology can be when used to study viruses.  Prime among these is one of T4 virus (Enterobacteria phage T4) infecting E coli; another magical one  from the same source is a depiction of the molecular motor which winds DNA into T4 heads.  A longer video has Michael Rossman, whose lab did the structural work behind the videos, explaining how the phenomenon could be useful in understanding viruses like herpesviruses in humans, which also appear to have molecular motors for DNA delivery – and, of course, how we can mess with them.

Self-assembly of viruses is also a good topic for video – and the full-length  Seyet T4 video is stunning in this regard.  So too is this one, showing a PhiX174 microvirus particle assembling.  One of my favourites, though, is the simplest: this is the depiction of how simple shapes can be induced to self-assemble into a virus-like particle - just by shaking.

I suppose, like everything, you get what you pay for with YouTube: which is nothing, most of the time.

But every now and then, a gem – which is what makes it fun to look.  I’m off to hunt down a Rolling Stones video virus replication videos!


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