Tag: crispr

Gene Therapy

This is the first time human cells, engineered in this particular way, have been given back to a patient. The technology has got enormous potential to correct other conditions

2019-06-30: Germline Gene Therapy

means of correcting disease-causing nuclear and mitochondrial DNA mutations in gametes or preimplantation embryos have now been developed and are commonly referred to as germline gene therapy (GGT). We will discuss these novel strategies and provide a path forward for safe, high-efficiency GGT that may provide a promising new paradigm for preventing the passage of deleterious genes from parent to child.

2020-12-07: Cures

Both the Vertex/CRISPR and Bluebird techniques seem to work – and in fact, to work very well. There are now people walking around, many months after these treatments, who were severely ill but now appear to be cured. That’s not a word we get to use very often.

CRISPR

CRISPR allows for much better genetic engineering than previous approaches and is a huge deal. It even works in human cells. Probably Nobel prize material.
2015-06-11: 1000x CRISPR

It is now possible to record a human genome (differences relative to a reference is only 2 megabytes. This is instead of 9 terabytes for a human genome with image data. CRISPR improvements are getting to 1 off target in 1 in 100 trillion (10^14) to 1 in 10 million trillion (10^19)

2015-11-11: CRISPR is the real deal

Editas plans to deliver the CRISPR technology as a gene therapy. The treatment will involve injecting into the retina a soup of viruses loaded with the DNA instructions needed to manufacture the components of CRISPR, including a protein that can cut a gene at a precise location. To treat LCA, the company intends to delete 1000 DNA letters from CEP290 in a patient’s photoreceptor cells.

2015-11-12: CRISPR Monsanto Problem

CRISPR is far too important to become entangled in the same web of confusion that has made G.M.O.s such a toxic issue. We ought to have learned something from those troubling and extended shouting matches; scientists, politicians, and everyone else needs to join in on this debate now. Society has no choice but to come to terms with both the potential benefits and the possible risks. That will require a big change: today, there isn’t even really a regulatory mechanism capable of governing products like CRISPR.

2016-03-09: Improvements to CRISPR subtypes like Cpf1 and now Cas9 are happening very quickly. This should reduce errors and increase the power of these gene editing technologies.
2016-10-14: CRISPR corrects sickle cells

Sickle cell disease is a genetic disorder caused by a mutation in one of the hemoglobin genes, which causes deformation of red blood cells and results in occlusion of blood vessels, severe pain crises, and progressive organ injury. To correct the mutation that causes this disease, DeWitt et al. modified hematopoietic stem cells from sickle cell disease patients using a CRISPR/Cas9 gene editing approach. The authors showed that the corrected cells successfully engrafted in a mouse model and produced enough normal hemoglobin to have a potential clinical benefit in the setting of sickle cell disease.

2018-04-26: Improving CRISPR accuracy 10000x

The use of bridged nucleic acids to guide Cas9 can improve its specificity by over 10000x in certain instances — a dramatic improvement.

2019-02-27: Doudna on CRISPR

Do you think that the medical applications of CRISPR in themselves can inform basic science?

For sure. CRISPR technology has been widely adopted by all kinds of scientists, including people like me. I was never doing anything with genome editing before CRISPR came along.

In my lab we’ve had a project over the last few years working on Huntington’s chorea, a degenerative neurological disease. The mutation that causes the disease is a single codon — 3 base pairs in the DNA — that gets repeated many times. If the codon gets repeated too many times, it leads to a defective protein that causes this disease. That’s been known for a long time, but the challenge was, how do you fix it?

We’ve been working on a way to deliver the CRISPR into mouse neuronal cells to make the necessary edits. But one of the curious things that’s come out of that line of work is that we found that only neuronal cells in the mouse brain were getting edited, not [the supportive glial] cells called astrocytes.

These cells are a lot smaller, so it could be that they don’t have enough surface area to take up the CRISPR protein efficiently. Or maybe they don’t respond to DNA cutting and editing in the same way as other cells.

2019-03-01: CRISPR error rates. Gene Editing Is Trickier Than Expected

how many errors are too many? Cells are prone to making their own mistakes—on the order of 1 every 1M-100M base pairs, with more for skin cells, and fewer for sperm and eggs. Does it matter if an overactive gene editor makes that number closer to 1 in 500K?

2019-05-07: CRISPR Inhibitor

The number of stories and journal articles about how CRISPR DNA-editing technology works, has worked, and is planned to work are beyond counting. How about an article about how to stop it in its tracks? That’s this one, just published in Cell from a multicenter team in Cambridge and New York. It describes a screening program for small-molecule inhibitors of S. pyogenes Cas9 (spCas9), because one would want some ways (not all of which currently exist) to turn its effects off in given places and at given times.

2019-10-04: CRISPR documentary

The teaser zooms in on the stomach-stabbing self-experimentations of biohackers like Josiah Zayner and Aaron Traywick. DIY Crispr is just one subplot in the larger narrative about what happens when nature can be minutely controlled, when humans might even preside over their own evolution. Their cameras also follow scientists like Jennifer Doudna and Kevin Esvelt and the first patients in an experimental gene therapy trial to treat hereditary blindness. “Our main hope is to create a discussion around these technologies. People might come away excited. Or they might be scared. But at least that means they’re talking and learning and understanding what’s coming.”

2019-12-18: CRISPR in Humans?

One of the most compelling arguments against CRISPR gene editing, namely the potential for misuse, can also be considered the most compelling argument for CRISPR gene editing. Banning progress on gene editing technology may create a black market, but the continuation of research on gene editing will allow the scientific community to control its use and ensure patient safety

2022-03-07: Another similar claim of a 4000x improvement. The new paper doesn’t mention BNANC, so who knows if these improvements stack. Probably not.

Researchers discovered how some of these errors can happen. Usually, the Cas9 protein is hunting for a specific sequence of 20 letters in the DNA code, but if it finds one where 18 out of 20 match its target, it might make its edit anyway. To find out why this occurs, the team used cryo-electron microscopy to observe what Cas9 is doing when it interacts with a mismatched sequence. To their surprise, they discovered a strange finger-like structure that had never been observed before. This finger reached out and stabilized the DNA sequence so the protein could still make its edit. Having uncovered this mechanism, the team tweaked this finger so that it no longer stabilized the DNA, instead pushing away from it. That prevents Cas9 from editing that sequence, making the tool 4000x less likely to produce off-target mutations. The team calls the new protein SuperFi-Cas9.


2023-01-19: CRISPR Cas12a2

“With this new system we’re seeing a structure and function unlike anything that’s been observed in CRISPR systems to date”.

While other CRISPR systems bind to their target sequence, make their cut, and then stop, when Cas12a2 binds to its target, it seems to “activate,” transforming in shape.

“It’s a change in structure that’s extraordinary to observe — a phenomenon that elicits audible gasps from fellow scientists”. Once activated, the protein can bind to any genetic material that comes near it, whether its single-stranded RNA, single-stranded DNA, or double-stranded DNA. Cas12a2 then starts shredding the material, making multiple cuts in indiscriminate locations.

Because the genetic material can belong to the bacteria itself, the result can be cellular death. CRISPR causes the infected cell to self-destruct — rather than let it become a virus factory.

2023-04-01: A much better drug delivery

Microbiologists were learning more about an unusual group of bacteria that use molecular spikes to pierce a hole in the membranes of host cells. The bacteria then transport proteins through the perforation and into the cell, exploiting the host’s physiology in their favor. Using the artificial-intelligence program AlphaFold, which predicts protein structures, the team designed ways to modify the tail fibre so that it would recognize mouse and human cells instead. They then loaded the syringes with various proteins, including Cas9 and toxins that could be used to kill cancer cells, and delivered them into human cells grown in the lab, and into the brains of mice. Similar to the early days of CRISPR–Cas9 research, the bacterial syringes are studied by only a handful of labs, and their roles in microbial ecology are only beginning to be understood.

2023-12-15: There are far better technologies like base and prime editing, than CRISPR.

That’s really what inspired us to develop base editing in 2016 and then prime editing in 2019. These are methods that allow you to change a DNA sequence of your choosing into a different sequence of your choosing, where you get to specify the sequence that comes out of the editing process. And that means you can, for the first time in a general way, programmable change a DNA sequence, a mutation that causes a genetic disease, for example, into a healthy sequence back into the normal, the so-called wild type sequence, for example. So base editors work by actually performing chemistry on an individual DNA base, rearranging the atoms of that base to become a different base.

Mosquito Gene Drive

Engineered sterile male mosquitoes
Brought down mosquito population in a test run in small town by 85% in 4 months.

2016-02-17:

Obviously there are some risks here, but risks have to be weighed against benefits – if we don’t do it, mosquito-borne diseases keep killing 1M people each year.

2016-07-15:

Today, worldwide, 3000 people will die of mosquito borne illnesses. 3500 will die in auto accidents. I don’t have good numbers to scale the problem of hospital errors globally — but I’m guessing between 5000 and 20000 deaths a day. These problems are easy or at least easy-ish to fix. The medical profession can break the culture of “let’s wing it” and “who has time to wash their hands?” in hospitals. It is possible to get rid of the mosquitoes that carry malaria, dengue, zika and the rest. The technology to deliver self-driving cars is close.

There are loads more real problems that kill people in huge numbers that have easy-ish ways to fix that I can name. By contrast, the terrorist attack yesterday was a single, small incident. Terrorism kills very few people.

2016-10-06: Wow, awfully clever name.

Bad mosquitoes spread disease. Good mosquitoes can stop them. Debug is a group of scientists and engineers developing technology to raise and release sterile mosquitoes to eliminate the ones that carry disease.

2016-10-08: The anti-vaxxers found a new hobby.

If the Keys scuttle the project, it may go against broader public opinion. A national survey found that 78% supported using GMO mosquitoes to fight Zika. Last month a bipartisan group of 61 Florida state legislators issued a statement asking the FDA to use emergency powers to give them Oxitec right now. “What’s happened now is you have various mosquito districts saying, ‘Why can’t we use this technology?’ ” If the vote goes against Oxitec, “we would move the trial somewhere else. But obviously it would be more preferable and more convenient to do it where we planned to do it.”

2022-07-04: Changing host smell

Some diseases can change how their hosts smell. Certain viruses and microorganisms have evolved to use this to their advantage. For instance, plants that are infected with the Cucumber mosaic virus release a molecule that attracts aphids, which the virus uses as a vector to infect new plants. Parasites that cause malaria advertise their hosts to passing mosquitoes through changes in body odor. Mice infected with Zika or dengue produced 10x as much acetophenone as did healthy mice. Daubing healthy mice — and a few human volunteers — with acetophenone revealed that mosquitoes were drawn to the smell. Giving infected mice vitamin A, which is commonly used to treat skin conditions, helped to lower the amount of acetophenone the animals exuded, potentially providing a new way to control the spread of both diseases.

2022-11-26: Data from a new field trial

treated mosquito populations were suppressed by 88-96%. Male mosquitoes have short lifespans as it is—just seven to 10 days—and the self-limiting trait becomes less prevalent in each subsequent generation of males. Eventually, it fades within the gene pool. That means more releases are needed.

Cancer

Personalized Cancer Treatment

The team solved the problem of delivery of siRNAs into cells by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA’s negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.

2013-07-16: Cancer uses ancient genes

We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells. It is rather like Windows defaulting to ‘safe mode’ after suffering an insult of some sort. The new theory predicts that as cancer progresses through more and more malignant stages, it will express genes that are more deeply conserved among multicellular organisms, and so are in some sense more ancient. Genes that are active in the embryo and normally dormant thereafter are found to be switched back on in cancer. These same genes are the ‘ancient’ ones, deep in the tree of multicellular life.

2014-05-17: Measles Virus as a Cancer Fighter. Remarkable: fighting one scourge with another.

2015-03-14: Cancer Cell Mutations

1 study of kidney cancers found that no 2 patients had exactly the same set of genetic mistakes; in fact, no 2 tumors within the same patient had the same mutations. Taking it one step further, 1 high-resolution DNA-sequencing study of breast cancer couldn’t find 2 cells within 1 tumor that were genetically identical

2015-08-26: Reprogramming cancer cells. Apply a large grain of salt to the claim, but the mechanism is still very interesting.

miRNAs orchestrate whole cellular programs by simultaneously regulating expression of a group of genes. The investigators found that when normal cells come in contact with each other, a specific subset of miRNAs suppresses genes that promote cell growth. However, when adhesion is disrupted in cancer cells, these miRNAs are misregulated and cells grow out of control. Restoring normal miRNA levels in cancer cells can reverse that aberrant cell growth.

2015-09-23: Dark matter cancer? This is pretty much speculation, but interesting speculation.

We can thus speculate that the mirror micrometeorite, when interacting with the DNA molecules, can lead to multiple simultaneous mutations and cause disease

2016-03-07: Winning the Cancer War

Unfortunately, we’re still stuck in dogma. We continue to live in a world where the standard of cancer care is built on the naïve, almost arrogant, assumption that simply understanding the gene is the only important thing. Or that understanding 50 genes or even 500 genes will give us all the information to unlock the secrets of cancer cell metastasis. But our research is beginning to show that this is no longer the case. The bottom-line is that the biology of cancer is extraordinarily complex. It’s so complex that the output of the gene—specifically, the downstream networks of proteins within our bodies—is even more important than the gene itself.

2016-11-18: CRISPR for lung cancer

Scientists at Sichuan University have injected a person with aggressive lung cancer with cells modified using the gene-splicing technology in a bid to make the patient’s immune system more effective at combating cancer cells.

2017-11-08: Cancer survival

cancer death rates continue to fall across most cancer types. From 2010 to 2014, overall death rates decreased by 1.8%. 5-year survival rates for most common types of cancer have increased quite significantly in the past 30-40 years.

2018-08-02: Cancer progress

Official statistics say we are winning the War on Cancer. Cancer incidence rates, mortality rates, and 5-year-survival rates have generally been moving in the right direction over the past few decades.

More skeptical people offer an alternate narrative. Cancer incidence and mortality rates are increasing for some cancers. They are decreasing for others, but the credit goes to social factors like smoking cessation and not to medical advances. Survival rates are increasing only because cancers are getting detected earlier. Suppose a certain cancer is untreatable and will kill you in 10 years. If it’s always discovered after 7 years, 5-year-survival-rate will be 0%. If it’s always discovered after 2 years, 5-year-survival-rate will be 100%. Better screening can shift the % of cases discovered after 7 years vs. 2 years, and so shift the 5-year-survival rate, but the same number of people will be dying of cancer as ever.

This post tries to figure out which narrative is more accurate.

and another perspective:

Death rates from the disease in the US dropped in the 2016-2017 period by their largest recorded %. This is unequivocally good news, and is attributed to advances in treatment – specifically, the advent of immunotherapies and of various targeted agents for lung and skin cancer. It may come as a surprise to some, but these death rates have actually been falling since the early 1990s at ~1.5% a year, a good part of which can be attributed to the decline in smoking. But the 2016-2017 decline bumped up to 2.2%, which has never been seen before

2019-08-20: Cancer Speciation

Aggressive cancers can spread so fiercely that they seem less like tissues gone wrong and more like invasive parasites looking to consume and then break free of their host. If a wild theory recently floated in Biology Direct is correct, something like that might indeed happen on rare occasions: Cancers that learn how to roam between hosts may gradually evolve into their own multicellular species. Researchers are now scrutinizing a peculiar group of marine parasites called myxosporeans to see whether they might be the first known example.

2021-05-22: Starving Cancer

Scientists are unraveling the molecular pathways by which slashing calories or removing a dietary component can bolster the effects of drugs. In mice with cancer, the effects are oftentimes on the same order of magnitude as those from the drugs that we give patients. If those trials show the ketogenic diet helps curb tumor growth for 2 years longer than the PI3K inhibitor otherwise would, the diet could become the standard of care. “That will be what physicians will tell patients to do.”


2022-08-14: Tumors recruit the nervous system to help them spread.

“The nervous system controls everything in normal tissues—growth or atrophy, or anything else”. So there’s a reason to believe that the same is happening with malignancies. “Cancer tissue grows fast so it needs the support of the nervous system”. Moreover, scientists know that certain cancers have a particular predilection for nerves. “For example, breast and prostate tumors have a propensity to look for nerves and kind of invade and travel through those nerves. That suggests that there is synergy there.”

The observational knowledge suggests that a greater amount of nerves bunching up around a tumor signals grimmer prognosis. For example, when pathologists assess the severity of prostate cancer, the number of nerves that surround these tissues factors in. “The pathologist will score that, and if there’s a lot of nerves in the area, it usually means a worse, or a more urgent situation. To us, that seems like a blind spot or a missing link.”

2022-11-23: Cancer vaccines?

After several decades, therapeutic cancer vaccines now show signs of efficacy and potential to help patients resistant to other standard-of-care immunotherapies, but they have yet to realize their full potential and expand the oncologic armamentarium. Here, we classify cancer vaccines by what is known of the included antigens, which tumors express those antigens and where the antigens colocalize with antigen-presenting cells, thus delineating predefined vaccines (shared or personalized) and anonymous vaccines (ex vivo or in situ). To expedite clinical development, we highlight the need for accurate immune monitoring of early trials to acknowledge failures and advance the most promising vaccines.

Antibiotics

For all you antibacterial soap-using dummies.

Unlike (soap and other) traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria. Alcohol-based hand sanitizers are just about as effective against germs as soap and water. They’re also easier on your skin than hand-washing, and unlike antibacterial soaps, they don’t breed antibiotic-resistant superbacteria.

The bottom line is that you shouldn’t live in fear of high-traffic surfaces. This type of contact simply isn’t the way people get sick.

2010-11-08: We are essentially back to an era with no antibiotics

This new resistance pattern has been reported in many different types of bacteria compared to previously and 10% of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials.

2015-01-08: New Antibiotics Platform?

A lot of people have had similar ideas to this one, based on the fact that the overwhelming majority of bacteria in any given environmental sample can’t be readily cultured. These organisms may well be able to produce useful antibiotics and other natural products, but how will you ever be able to tell if you can’t fish any of them out? Using this on a soil sample from Maine and leaving the chip in situ for a month, a number of colonies formed. These were tested for their ability to grow outside the device in fermentation broth, and extracts of these were tested against pre-grown lawns of an S. aureus strain to look for useful antibiotic activity. Lo and behold, one extract cleared out a large spot – it turned out to come from a newly described bacterium (Eleftheria terrae, provisionally). The compound present has been named teixobactin, and here it is. So how useful is the compound? It’s active only against gram-positive organisms, which is too bad, because we could really use some new gram-negative killers (their cell membranes make them a tougher breed). But the mechanism of action turns out to be interesting: studies of S. aureus with labeled precursors showed that teixobactin is a peptidoglycan synthesis inhibitor, but extended exposure and passaging did not yield any resistant strains. That’s close to impossible if an antibiotic is binding a particular protein target – stepping on the selection pressure will usually turn up something that evades the drug. When you don’t see that, it’s often because there’s some nonspecific non-protein-targeted mechanism, which can be problematic, but teixobactin isn’t toxic to eukaryotic cells in culture (and has a favorable tox profile in mice as well). It turns out that it binds to some of the peptidoglycan precursors, lipid II and lipid III. Vancomycin has a similar mechanism (binding to lipid II), but teixobactin has a wider spectrum of activity against lipid II variants (and lipid III as well). This mechanism makes developing resistance not so straightforward – the selection pressure is more of a bounce shot than a direct hit.

2015-02-24: Antibiotics market failure

we seem willing to pay $100K or more for cancer drugs that cure no one and at best add weeks or a few months to life. We are willing to pay 1$0Ks for knee surgery that, at best, improves function but is not lifesaving. So why won’t we pay $10K for a lifesaving antibiotic?

2015-03-31: Medieval salve kills MRSA. Impressive! Not all ancient medical knowledge is homeopathic nonsense.

Take cropleek and garlic, of both equal quantities, pound them well together… take wine and bullocks gall, mix with the leek… let it stand 9 days in the brass vessel

So goes a 1000-year-old Anglo Saxon recipe to vanquish a stye, an infected eyelash follicle. If the 9th Century recipe does lead to new drugs, they might be useful against MRSA skin infections such as those that cause foot ulcers in people with diabetes. These are usually antibiotic-resistant

2016-01-23: Antibiotics synthesis

Antibiotics are generally synthesized in nature by bacteria (or other microbes) as defenses against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Almost all bacterial species cannot be grown in the lab using practical methods. That hasn’t changed for decades. But those bacteria grow fine in the environment, typically the soil. So… can we isolate antibiotics from the soil?

2018-05-21: Phage Therapy

3 months earlier, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying. … “We are running out of options to save Tom. What do you think about phage therapy?”

2019-11-04: CRISPR Antibiotics

An alarming number of bacteria are now resistant to one or more antibiotics, so this new line of inquiry would certainly be welcomed if it proves effective.

In their recent study, Dr. Edgell and his colleagues successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. By programming the Cas9 to view the bacterium itself as the enemy, Dr. Edgell and his colleagues were able to force Salmonella to make lethal cuts to its own genome.

As we discover more of the benefits of our microbiota, it would also be interesting to have a solution to bacterial infections which doesn’t create problems for our “good bacteria.

2020-02-22: Antibiotics ML

So overall, this is an impressive paper. The combination of what appears to be pretty rigorous ML work with actual assay data generated just for this project seems to have worked out well, and represents, I would say, the current state of the art. It is not the “Here’s your drug!” virtual screening of fond hopes and press releases, but it’s a real improvement on what’s come before and seems to have generated things that are well worth following up on. I would be very interested indeed in seeing such technology applied to other drug targets and other data sets – but then, that’s what people all around academia and industry are trying to do right now. Let’s hope that they’re doing it with the scope and the attention to detail presented in this work.

2020-07-24: SCH-79797

Researchers have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance. This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance

2020-08-07: Maybe the non-profit route will work

If something isn’t done now, antibiotic-resistant bacteria could kill as many as 10M people a year by 2050. A little-known Boston nonprofit could be our best hope.

2021-07-28: Biofilms are nasty

This discovery underscores how important it is to include biofilms in any studies of antibacterial compounds because being able to kill planktonic cultures bears no relation to being able to break down biofilm.

2021-10-14: Another approach is to modify bacteria to destroy the MSRA biofilms

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

2023-05-23: Odd that phage therapy only made progress in former soviet republics

“Phages” are little known outside the former countries of the Soviet Union, which did the most to develop the idea. In Georgia they have been part of the local pharmacopoeia for decades. (Indeed, 2023 marks the Eliava’s centenary.) Little vials containing stale-tasting liquid full of anti-bacterial viruses can be bought at pharmacies across Tbilisi. Now, as worries about antibiotic resistance build, Western firms are taking a second look.