#phage edits

[phagechildon]

I couldn't stop thinking of Hualian when listening to this song so I finally edited to it ;/////; It's always been Xie Lian, and it's always been Hua Cheng ;////;

Song: It's Always Been You Artist: Phil Wickham Donghua: Heaven Official's Blessing Art: English Novel Art by ZeldaCW

[harshr]

Records now available via Phage Tapes! Three different cover art variations plus an extra-special limited Test Press version. Includes a bonus track not on the regular digital version plus a full lyrics sheet.

[gengarghast]

I liked sparklecare until the author did this odd thing where villainous or morally questionable characters are always strictly cishet and even said it was their hard-line rule? Like LGBT characters can never be antagonists or abusive which just felt weird to me, maybe they relaxed on that though I dunno? I am def never offended if a villain shares my gender in a series where good guys can be like me anyway I mean

TLDR: Yeah, there's some weird gender bias with the characters sometimes. Anyways, *starts talking about Awful Hospital again*

Also, spoilers for both Sparklecare Hospital and Awful Hospital. (up to page 41 of SH and various plot point/character reveals for Awful Hospital)

I haven't read too far into the comic myself to confirm, and the genders of the characters were kind of vague anyways thanks to Nurse Mood's shitty notetaking (EDIT: I learned about the existence of the 'Cast' page, my bad), but yeah I've definitely seen a pattern where the LGBT characters are all 'good', regardless of whether they're a patient or employed by the hospital.

For example, Mood and Ms. Dies are in a lesbian relationship. They're also both employed by the hospital, and despite this are portrayed sympathetically, in opposition to Dr. Cuddles' being genuinely malicious and cruel, as seen below:

...Even though it's also shown that Mood doesn't give half a shit about the patients, either.

Now, if you want some equal, well-handled representation, look no further than seriously one of the worst best webcomics of all time...

Awful Hospital, despite the majority of its cast not even being remotely human, has some great LGBTQ representation in both it's heroes and its villains! Well, 'villains'. The only real villain is the Big Bad(s) of the series, everyone else is just doing what they gotta do in order to survive.

Speaking of which, this is E.M. Balmer. He's a villain of a whole arc, and has a sort of "kid's cartoon villain" vibe. Goofy, incredibly self-absorbed, and affably evil. He's also implied to have some sort of interest in another male character, Dr. Phage.

Also, just tell me this beefcake isn't some sort of a Gay. Just look at him.

...AAAANYWAYS, in terms of heroic queer characters, you've got your choice between the Lesbians and the Trans.

Celia and Staph are this really sweet fungal/bacterial couple who have like a trillion kids and are also besties with the person who's corpse they live in.

Miss is cleverly implied to be trans with this line here:

Which, personally, I think is really cool!!!!

ALSO I JUST REMEMBERED, THERE ARE ALSO SCISSORS WHO ARE LESBIANS! AND ALSO THESE STAIN MOMS

Also, I realize I didn't really talk much about how cool and epic Awful Hospital's LGBTQ+ characters are very much, buuuut that's because I'm tired and need to sleep so whatever

Anyways, goodnight tumblr people, and...

Read Awful Hospital for fuck's sake!!!

[oldschoolfrp]

Shadow Knight, Michael Kucharski cover painting, supplement for the Amber Diceless Role-Playing game edited by Erick Wujcik, Phage Press, 1993

[dianaladrislovebot]

my book annotations : book 2 edition - hunger

hey there yall it’s time for bookmarks part 2 i forgot to do this before my apologies,,, these still aren’t funny but that’s entirely because the entire books plot happens within the last 100 pages i promise it will get better at some point

‘diana was pitiless. “what, are you stupid now as well as crazy?”’ - get him baby girl (hunger, page 13)

‘“anyway, i might look good with just two hairs,” sam said. he looked at his reflection in the glass front of the microwave.’ - why is bro checking himself out (hunger, page 25)

‘“you’d like that, wouldn’t you diana? me fighting caine. sorry to disappoint you. i am 100% loyal to caine. we’re like brothers, the two of us. not like him and Sam, more like blood brothers,” he winked at her.’ - don’t lie drake you’re in love with him (hunger, page 41)

‘he didn’t look strong. he looked like a dweeb.’ - A DWEEB? LMFAO (hunger, page 55)

‘in the three months caine had spent hallucinating and yelling crazy stuff-‘ - my favourite basket case (hunger, page 79)

‘bug hadn’t just been sent to coates as a punishment; he’d been sent for his own safety.’ - god he’s a freak (hunger, page 80)

‘the boy evidently wanted the window open, but the battery was dead, so he drew a gun aimed it at the driver side window, and fired.’ - what’s wrong with him part 2 (hunger, page 90)

‘“i’m not anybody’s daddy,” sam practically snarled.’ - are you sure about that (hunger, page 104)

‘“you should be on our side, quinn. everyone knows you’re a normal,” another kid, lance, said. “well… kind of normal. you’re still quinn.”’ - homophobia ??? (hunger, page 216)

‘caine felt a flash of anger. josh was a kid, no more than ten. what was sam thinking, putting kids in this position?’ - is. is he serious. (hunger, page 251)

‘quinn was a little surprised by alberts matter of fact tone. he’d half expected a gollum-like, ‘my precioussss’, or something.’ - quinn what- (hunger, page 272)

‘“how’s it look?” caine asked. he laid his hand on jacks shoulder, a friendly gesture meant to reassure jack. for the first time in his life it occurred to jack that he wanted to spin around and punch caine. punch him hard.’ - DO IT JACK (hunger, page 285)

‘“let me explain something to you people. i’m not your parents. i’m a fifteen-year-old kid. i’m a kid, just like all of you. i don’t happen to have any magic ability to make food suddenly appear. it can’t just snap my fingers and make all your problems go away. i’m just a kid.”’ - and life is a nightmare (hunger, page 377)

‘“so we don’t drop it.” drake said finally.’ - he’s so impossibly stupid (hunger, page 447)

‘he smiled, patted drakes gaunt cheek-‘ - they’re so gay ????? (hunger, page 448)

‘“does he have a nickname?” diana went on remorselessly. “i mean, ‘gaiaphage’ is so long. can we call him phage? or maybe just g?” from outside came the sound of metal ripping, glass shattering. jack converting an suv into a convertible. “the ‘g’ monster.” diana said.’ - love of my life she’s so cute <3 (hunger, page 526)

‘his mouth was drawn into a grimace. it was the only time diana had ever looked at him and found him ugly.’ - DID SHE JUST CALL HIM UGLY (hunger, page 539)

‘brianna breathed hard. stared. there was a rushing waterfall in her ears. a roar. then a blur as the world around her screamed past and she hit caine with all the speed and fury at her command. caine went sprawling.’ - WOOOO BREEZE FOR THE WIN (hunger, page 558)

‘“you can’t buy me with food,” duck huffed. “i… i want a swimming pool too.”’ - there’s not going to be a swimming pool you stupid slut (hunger, page 559)

[fansenshialliance]

Join the Fan Senshi Alliance server and take part in the Galaxia Takeover event!

For the month of October, Galaxia rules the server and has stolen everyone's starseeds, leaving Animamates and Phages in her wake.

We are running a variety of contests with some prizes for the winners!

Draw/Design an Animamate version of an SMOC (doll makers allowed).

Draw/Design a Phage version of an SMOC (doll makers allowed).

Draw/edit or write a scene of your OC having their Starseed stolen.

Draw/design your OC's starseed (doll makers allowed).

Scavenger Hunt - find all the starseeds hidden in the server.

We've specially boosted the server to allow for a fun new banner and role icons (still being rolled out), and hope you join us to have some fun!

Join here!

[inventors-fair]

For each victor—a victory! ~

Our winners this week are @hypexion, @misterstingyjack and @nine-effing-hells!

@hypexion — Priestess of Ashtear

This card raises questions about the world that I enjoy exploring. Therosian or not, the concept of sorting through the ashes and bringing ghosts from the notions, whatever they may be, is solid. There's the entity of Ashtear (a new deity, or portmanteau?) that—well, 'ash' is right there, and perhaps it's the silver-grayness of it all, but I'm simply having an easy time getting the character's mojo settled clearly in my head. I think "dead" doesn't need to be in the flavor text for sentence flow, but the card's doing a great job in all other aspects of its presentation. There's a ghostliness that distinguishes it from the auras of Theros and the macabre of Orzhov.

Moreover, the delirium aspect is without delirium; it's precise, constructed, and counts for what is presented, not reaching for a specific number. We take what we can get. You'll probably end up with 3-4 spirits naturally, and for an uncommon, that's a solid late-game drop, perhaps even early-game if you can knock off both a removal spell early and an enchantment creature dying in combat. Very powerful as an aggressor and as a blocker to spread out the late game. Should the "create a..." part come before the "for each" clause, like how Avenger of Zendikar does? I think so, but don't let these small bumps take away from the fact that this card, in its simplicity, pulls off some tasty vibes.

@misterstingyjack — Mutilations Expert

I'll be a damned clown—"damaged creature" appears on exactly one Phage vanguard card, but it certainly appears. Is that precedent? It's precedent enough for me. The thing I like mechanically about this card is that on your turn, you can slide in that extra damage after your opponent thinks they've made a good block, and on your opponent's turn, they'll be calculating their attacks without calibrating for the surprise life loss. How long are damaged creatures going to be staying around? I suppose it all depends, but Footlight Fiend makes even your big boys stickaroundable for the flinging. Plus, with chump-blocking, this makes some combat tricks much better.

But Rakdos sacrificing its wounded creatures really is new territory for me to consider. Fresh meat is what it is, but the stabs make it all the more enticing. Truly, this is something that makes the deckbuilding a lot more complicated. How are you going to change up your gameplay? Will your opponents know? My guess: probably not. This card might not define an archetype but it could see waves in the right deck. It's certainly made me want to think about how to make it happen, y'know? Also, name: on point. Typeline: definitely on point. Aren't the Rakdos fun?

@nine-effing-hells — Undecided Undergrad

Now, I'll be honest: this is the card that I feel I have to defend the most. The flavor text needs heavy paring and editing, and the cost of the activated ability could be reduced IMO. Ward I'll defend just because—well, this student needs defending. The good news is that I played a helluva lot of Strixhaven, and moreover, this got me thinking about the incredible deck that could be made with this card. You and I both know that one person who's gonna get as much fixing and token generation as they can before drawing themselves out and having a blast doing it. It's not easy to get all five colors, but you can try. Getting a five-color token ain't a walk in the park either.

This card's got such a good feeling connected to its gameplay. Hugely positive, hugely inventive, and moreover, this card actively resists an archetype. I think I'm going to be going into the rest of the commentary with those considerations, genuinely! I think that there are some deckbuilding techniques that speak to people looking to solidify a concept, and some that speak to the weirdness and the fringe benefits of going in XYZ direction. If that's not wholly related to the mood that this card is bringing, I don't know what is.

Runners and commentary coming up. @abelzumi

[bootleg-sara]

Gonna be posting my art fight attacks lol. You never truly can escape me

First two where for my good friends @hootispootis and @asmaroth characters of "Deoxys" and Betty Phage! Both wonderful fellas

Some cute Unown fusions by Lorelai on toyhouse, Comic Relief by ExtraRare on toyhouse and N by NewtFish on instagram

[small edit] the transparent bg made Comic Relief’s eyebrows blend into the blackness akdbkabd

[phagechildon]

Stress edit cause everything's been too much lately and it helps~ Someday Xie Lian will be free from his tormentor, with San Lang's help~ Song: Lovely Artist: Billie Eilish and Khalid Donghua (anime): Heaven Official's Blessing ( Tian Guan Ci Fu ) or ( TGCF )

[jhavelikes]

Methods for the targeted integration of genes in mammalian genomes suffer from low programmability, low efficiencies or low specificities. Here we show that phage-assisted continuous evolution enhances prime-editing-assisted site-specific integrase gene editing (PASSIGE), which couples the programmability of prime editing with the ability of recombinases to precisely integrate large DNA cargoes exceeding 10 kilobases. Evolved and engineered Bxb1 recombinase variants (evoBxb1 and eeBxb1) mediated up to 60% donor integration (3.2-fold that of wild-type Bxb1) in human cell lines with pre-installed recombinase landing sites. In single-transfection experiments at safe-harbour and therapeutically relevant sites, PASSIGE with eeBxb1 led to an average targeted-gene-integration efficiencies of 23% (4.2-fold that of wild-type Bxb1). Notably, integration efficiencies exceeded 30% at multiple sites in primary human fibroblasts. PASSIGE with evoBxb1 or eeBxb1 outperformed PASTE (for ‘programmable addition via site-specific targeting elements’, a method that uses prime editors fused to recombinases) on average by 9.1-fold and 16-fold, respectively. PASSIGE with continuously evolved recombinases is an unusually efficient method for the targeted integration of genes in mammalian cells.

Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing | Nature Biomedical Engineering

[snugglebuddyhan]

Currently making builds for all the weapons in Warframe, since I have nothing else to do

This is a note to myself for which weapons I enjoyed playing the most for future reference.

Tested without the use of rivens or any other outside factors, except weapon arcanes

(Biggest r.i.p to me as an Ash main)

My favorite primary weapons:

Acceltra Prime (Already one of my mains)

Aeolak

Alternox (Have always liked it. Fun to shoot. Plus, it's huge and looks really cool. It's flashy and has one of the best designs in the game. It's reload animation is also fun)

Ambassador

Amprex (Long time favorite)

Argonak

Astilla Prime (Might main it. Edit: definitely maining it)

-----------------

Basmu (Stronger than I thought)

Baza Prime

Boar Prime

Boltor Prime

Bubonico

Buzlok

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Cedo (Used for a utility for melee priming, but realized it's primary mode is just as strong when you prime the enemies with it first. Eats through steel path enemies)

Convectrix (Fun to shoot)

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Dera Vandal

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Exergis (Can one shot level 200 heavy gunners without a single headshot, so might main)

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Fulmin Prime

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Glaxion Vandal (Fun to shoot)

Gotva Prime

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Hema (The heartbeat effect on reload is neat)

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Nagantaka Prime (Didn't like at first until I discovered its alt mode)

Naturak (I mean, I think?? I like it?)

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Phage (Move over, Astilla)

Phantasma Prime (Good steel path weapon)

Proboscis Cernos (It's fun watching enemies get snatched up. I mostly use it for a little crowd control)

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Quellor

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Sancti Tigris (Was my most played weapon for years)

Scourge Prime

Sobek (Was also a weapon I used for years)

Soma Prime (Another long timer)

Stahlta

Steflos (I'm in love with its reload animation. It's also fun to shoot, which I haven't been able to say about a lot of the weapons so far, even the ones I like)

Strun Prime

Synapse

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Tenora Prime

Tigris Prime

Trumna

Total amount of formas used: 561

Finished. Not listing Kuva and Tenet weapons until I re-farm them all with the proper elements. Same with incarnon weapon forms

The primary weapons I absolutely hated:

Afentis

Attica (Okay, it's not THAT bad)

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Carmine Penta (Any variant)

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Javlok

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Mutalist Cernos

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Sybaris (Any variant)

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Quanta Vandal

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Torid

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Zhuge Prime

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Pretty much every bow and sniper, except Daikyu or however you spell it. They aren't bad. I've made some pretty strong builds, so that's not the issue. I just don't care for them.....in this game

My top 10 most used primaries based on my overall profile stats:

Tenet Arca Plasmor (Haven't touched it in ages)

Ignis Wraith (I remember being called a noob in the squad chat by a legendary 1 player a few years ago for using this weapon and now as a legendary 4 I still use it. I don't get the superiority people hold above themselves, bc they don't participate in whatever the current meta is. It's never that serious. The weapon is good and it gets shit done. Of course I'm going to use it)

Sancti Tigris

Acceltra (Non prime version)

Amprex

Cedo (Used for priming)

Soma Prime

Sobek (Patiently waiting for a kuva varient. Edit: my prayers have been answered)

Phantasma Prime (Mostly used to kill eximus in steel path)

Alternox

My favorite secondary weapons:

Acrid (Corpus killer)

Afuris Prime (Saw a popular build on overframe say this weapon isn't worth it and is just mastery fodder and I have to respectfully disagree. It's extremely powerful. Can even shred steel path enemies, so.......)

Akarius Prime

Akjagara Prime (Really like this one. 10's across the board)

Aksomati Prime

Akstiletto Prime

Akvasto Prime

Arca Scisco

Athodai (Was worth doing railjack for)

-----------------

Catabolyst (I love it. I know it's early, but I'm thinking about maining it. Edit: Nope, my dumbass keeps forgetting I have to manually reload it. Just going around shooting nothing)

Cyanex

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Embolist

Epitaph (Perfect for disruption or slowing things in general)

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Hikou (Knew I was going to like it before I even finished modding it)

Hystrix

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Kompressa (Really fun. My equivalent to the Alternox and Steflos and how fun it is to shoot. Edit: It's the goat, actually. One of the strongest secondaries I've ever played with)

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Lex Prime (My second most used secondary)

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Magnus Prime

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Ocucor

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Pandero

Pox

Prisma Angstrum

Prisma Twin Gremlins

Pyranna

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Quatz

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Secura Dual Cestra (Been using the heck out of these bad boys)

Spira Prime

Staticor

Synoid Gammocor

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Twin Kohmak

Tysis

Total amount of formas used: 348

Finished. Just like the primaries, I'm not listing Kuva and Tenet weapons until I re-farm them all with the proper elements. Same with incarnon weapon forms

The secondary weapons I absolutely hated:

Aegrit

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Castanas (Sold them for credits immediately)

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Knell Prime (Yes, even despite how strong it is)

Kulstar

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Sancti Castanas (Joined his cousin)

Sonicor (Could be used for crowd control, but can't be bothered. Will probably sell it)

Stug (What the hell is that)

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Twin Viper Wraith

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Vaykor Marelok

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Zymos

My top 10 most used secondaries based on my overall profile stats:

Kuva Nukor (Used it for priming when I first got into steel path. Haven't touched it since. Plus, if I want to prime I'll use the cedo now)

Synoid Gammacor (Used it for years. Was my all time favorite weapon. Haven't used it in ages though)

Lex Prime (Was mostly used back when we didn't have exalted weapons we could mod separately, so I picked this weapon for Mesa's peacemaker ability)

Staticor (Obsessed with the way it shoots. It's charged mode is also cool)

Twin Grakatas (Don't remember using this tbh)

Akarius Prime

Tenet Cyrcon

Afuris Prime

Sporelacer (Okay, so this is actually my most played secondary. For some reason it's played percentage has been stuck on 1.3% usage for the past 2 years and won't budge. Really wish DE would do something about this, so my profile is actually accurate)

Pox (I like this weapon, but it's only here, bc it was the weapon I picked for an elite archimedea rotation that I kept going back into, so I could help people get the hidden sumdali. I didn't like my primary weapon rolls and I don't care too much for melee weapons, so I used this for my primary source of damage)

Favorite melee weapons so far. I'm not really a fan of swinging things around, but I'll try to make the most of it:

Argo & Vel

Arum Spinosa

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Broken War (Got me through steel path. Haven't really used it much since then)

[nicole1066]

The Perfect Predator

If you love reading about medical breakthroughs, you’ll love this memoir by Steffanie Strathdee. Her husband was the first person in the U.S. to receive phage therapy for his multi-drug resistant infection. None of it would have happened with her grit and determination. A riveting read. View at Medium.com https://medium.com/p/cca1d625e661/edit

[instantebookmart]

Novel Antimicrobial Agents and Strategies, ISBN-13: 978-3527336388 [PDF eBook eTextbook]    440 pages ISBN-13: 978-3527336388 ISBN-10: 9783527336388  Publisher: Wiley-VCH; 1st Edition (November 24, 2014)  Author(s): David A. Phoenix, Frederick Harris, Sarah R. Dennison Language: English   By integrating knowledge from pharmacology, microbiology, molecular medicine, and engineering, researchers from Europe, the U.S. and Asia cover a broad spectrum of current and potential antimicrobial medications and treatments. The result is a comprehensive survey ranging from small-molecule antibiotics to antimicrobial peptides and their engineered mimetics, from enzymes to nucleic acid therapeutics, from metallic nanoparticles to photo- and sonosensitizers and to phage therapy. In each case, the therapeutic approaches are compared in terms of their mechanisms, likelihood to induce resistance, and their efficiency in a global healthcare context. Unrivaled knowledge for professionals in fundamental research, pharmaceutical development and clinical practice. Professor David Andrew Phoenix studied Biochemistry at degree and doctoral level at Liverpool University which in 2009 awarded him a Doctor of Science for his impact on the field. In 2000 he was appointed Professor of Biochemistry, at the University of Central Lancashire (UCLan) and has held visiting chairs in Canada and Russia. He has drafted over 150 papers as well as a number of edited collections and monographs. He is a Fellow of the Royal Society of Chemistry, The Society of Biology, The Institute of Mathematics and Its Applications and the Royal Society of Medicine. Since 2008 he has been the Deputy Vice Chancellor of UCLan and also chairs a research institute in Shenzhen focused on nanotechnology and biomedical engineering. He was made an Officer of the Most Excellent Order of the British Empire in 2010 for services to Science and Higher Education and recognized as an Academician by the Academy of Social Sciences in 2012. Dr. Frederick Harris studied at UCLan, graduating with a Bachelor of Science in Biochemistry and Microbiology in 1993 before gaining his Doctorate for work on the penicillin-binding proteins of Escherichia coli in 1998. Subsequently, he has undertaken research at Utrecht University and the Leibniz-Centre for Medicine and Biosciences, Germany. In 2000, Frederick started as a Research Fellow at UCLan and now has more than 75 publications to his name, which primarily focus on antimicrobial and anticancer peptides. Dr. Sarah Rachel Dennison graduated from the University of Wales, Bangor with a Bachelor of Science in Environmental Biology in 1999. Subsequently, she undertook postgraduate research in Biochemistry / Biophysics, which led to a doctorate in 2004. Currently, Sarah is a Research Associate in the School of Pharmacy and Biomedical Sciences at UCLan where she is investigating the role of amphiphilicity in the function of antimicrobial peptides using a number of biophysical techniques. What makes us different? • Instant Download • Always Competitive Pricing • 100% Privacy • FREE Sample Available • 24-7 LIVE Customer Support

[hifivefashion]

Moon Phages

[laocommunity]

Revolutionizing Gene Editing: The Incredible Potential of Bacteriophage T4-based Artificial Viral Vectors

Revolutionizing Gene Editing: The Incredible Potential of Bacteriophage T4-based Artificial Viral Vectors Revolutionizing Gene Editing: The Incredible Potential of Bacteriophage T4-based Artificial Viral Vectors Gene editing has been a popular topic in the field of genetics for many years. Scientists have been studying and developing new ways to edit genes to treat different diseases and conditions. Bacteriophage T4-based artificial viral vectors have been identified as powerful tools that could revolutionize gene editing. With the help of T4-based vectors, we can modify genes more easily, accurately, and inexpensively than ever before. What are Bacteriophage T4-based Artificial Viral Vectors? Bacteriophage T4-based artificial viral vectors are a type of virus that can be used as a tool to modify genes. Bacteriophages are viruses that infect bacteria. They contain a genetic material that can be easily inserted into the bacteria's genome, and once inside, they take control of the bacteria's machinery to produce more phages. T4 is a bacteriophage that specifically targets E. coli bacteria, which is a commonly used model organism in genetic engineering. The T4 phage is made up of a head that contains its genetic material, and a tail that allows it to attach to and infect the E. coli bacteria. T4-based vectors are created by removing the phage's genetic material and replacing it with a desired sequence of DNA. Benefits of Using T4-based Vectors One of the main benefits of using T4-based vectors is their ability to deliver genes to cells more effectively than other methods. T4 phages have evolved over millions of years to specifically target E. coli bacteria, so they are highly efficient in their ability to infect and deliver genes to these cells. This means that they can deliver genes to target cells with much greater efficacy than other genetic delivery methods such as electroporation or micro-injection. Another benefit of T4-based vectors is their safety. T4 phages are natural viruses that are commonly found in the environment, so there is no risk of causing an immune response in patients. This makes them ideal for gene therapy, where the immune system's response to foreign material can be a significant hurdle. Additionally, T4-based vectors are relatively easy and inexpensive to produce. Traditional virus-based gene therapy often requires large amounts of virus to be produced, which can be costly and time-consuming. In contrast, T4 phages can be grown in large numbers in standard E. coli cultures, making them a low-cost and highly scalable option for gene delivery. Applications of T4-based vectors The potential applications of T4-based vectors are vast and varied. They can be used for gene therapy, where they can be used to replace or modify genes in a patient's cells to treat genetic diseases. They can also be used in synthetic biology to modify cells and organisms for research or industrial purposes. Additionally, they can be used in gene editing to modify specific genes in cells for research or therapeutic purposes. The Future of T4-based Gene Editing The future of T4-based gene editing is promising. Scientists are constantly discovering new ways to use T4 phages to deliver genes and modify cells. New modified versions of T4 phages are being developed that can efficiently infect other bacteria and even mammalian cells, opening up new avenues for gene delivery. In conclusion, Bacteriophage T4-based viral vectors offer great potential for revolutionizing gene editing. Their ability to deliver genes more effectively, their safety, and their cost-effectiveness make them an ideal tool for research and therapeutic purposes. As our knowledge and technology in the field of genetics continue to advance, we can expect to see even more exciting developments in the use of T4-based vectors for gene editing. #HEALTH Read the full article

[tastydregs]

Gene editing makes bacteria-killing viruses even more deadly

Broad-spectrum antibiotics are akin to nuclear bombs, obliterating every prokaryote they meet. They're effective at eliminating pathogens, sure, but they're not so great for maintaining a healthy microbiome. Ideally, we need precision antimicrobials that can target only the harmful bacteria while ignoring the other species we need in our bodies, leaving them to thrive. Enter SNIPR BIOME, a Danish company founded to do just that. Its first drug—SNIPR001—is currently in clinical trials.

The drug is designed for people with cancers involving blood cells. The chemotherapy these patients need can cause immunosuppression along with increased intestinal permeability, so they can't fight off any infections they may get from bacteria that escape from their own guts into their bloodstream. The mortality rate from such infections in these patients is around 15–20 percent. Many of the infections are caused by E. coli, and much of this E. coli is already resistant to fluoroquinolones, the antibiotics commonly used to treat these types of infections.

The team at SNIPR BIOME engineers bacteriophages, viruses that target bacteria, to make them hyper-selective. They started by screening 162 phages to find those that would infect a broad range of E. coli strains taken from people with bloodstream or urinary tract infections, as well as from the guts of healthy people. They settled on a set of eight different phages. They then engineered these phages to carry the genes that encode the CRISPR DNA-editing system, along with the RNAs needed to target editing to a number of essential genes in the E. coli genome. This approach has been shown to prevent the evolution of resistance.

After testing the ability of these eight engineered phages to kill the E. coli panel alone and in combination, they decided that a group of four of them was the most effective, naming the mixture SNIPR001. But four engineered phages do not a drug make; the team confirmed that SNIPR001 remains stable for five months in storage and that it does not affect any other gut bacteria.

The researchers showed that SNIPR001 was well tolerated in Göttingen minipigs—after oral administration, the pigs did not exhibit any clinical, biochemical, hematological, or immunological effects, and no phages were found in their blood, so there was no systemic exposure. In mice, oral administration of SNIPR001 reduced the amount of target E. coli in the feces, and none of the recovered E. coli were resistant to the phage cocktail.

Phage therapy, tempting though it is in theory, has a checkered history at best. But SNIPR BIOME’s goal of using CRISPR to precisely target only harmful bacteria may revitalize this technique, allowing us to continue vanquishing our bacterial foes without promoting drug resistance.

Nature Biotechnology, 2023. DOI: 10.1038/s41587-023-01759-y