Javier Dalmendray

PhD student @UF_MCS

[Nian Wang @NWangUF]

Immune activation by a phloem-colonizing plant pathogen drives citrus Huanglongbing disease development: Cell Host & Microbe https://t.co/l12R63h3Gi Glad to share our recent progress on citrus HLB. Kudos to the co-first authors Xianen, Wenxiu, Wenting, and Yu and other colleagues in my lab. It is truly a team work by collaboration with Allison K. Hanse at UCR, Ning Zhang at JMU, and Madhurababu Kunta at TAMUK.

[Nian Wang @NWangUF]

https://t.co/8OTyJnFmi1. Glad to see our CRISPR technology doing the job.

[Matthew R. Willmann @PlntTransformer]

Terrana Biosciences is looking for an expert in plant viroids to join our team in Durham, North Carolina! https://t.co/6NSLCLtf6C

[Matthew R. Willmann @PlntTransformer]

I am looking to hire a Senior Scientist in Plant Virology to join the Terrana Biosciences team in Durham, North Carolina. https://t.co/u0yShAAcm4

[Matthew R. Willmann @PlntTransformer]

Please retweet: Job opening for a Scientist for the Terrana Biosciences’ Delivery and Transformation team. This position is based in Raleigh, North Carolina. For more information or to apply: https://t.co/lEUlB5LAmL

[Arc Institute @arcinstitute]

🧬Introducing a powerful, programmable new mechanism for genome design: DNA recombination with bridge RNAs.

As the first natural RNA-guided DNA recombinase, this system enables insertion, excision, or inversion of any two DNA sequences.

Out today in @Nature, led by Arc scientists @pdhsu, @mgdurrant, and @ntperry13 🧵

Read more: https://t.co/fmL8ZefOyw
Image by @visualscience

[Patrick Collison @patrickc]

This morning, Nature published two papers on bridge editing, the new genome engineering technology from @ArcInstitute: https://t.co/IL23V7nYoW, https://t.co/tOE10YZakn. I'm quite excited about its potential!

Since the whole thing is pretty arcane, I fed the blog post (https://t.co/tZZWNRUBdU) to Claude 3.5, and asked it to write an introduction. Below is the rather impressive (unedited) result.

Genome Design: The Bridge to Our Biological Future

I.

Imagine you're trying to edit a document, but instead of a cursor, you have a pair of scissors. You can cut out words you don't like, maybe paste in a few new ones, but precise editing? Forget about it. Now imagine someone hands you a pen. Suddenly, you can write whatever you want, wherever you want. This is the kind of leap we're seeing in the world of genome editing.

For the past few decades, we've been snipping away at genomes with tools like CRISPR, making impressive progress but always constrained by the fundamental nature of our tools: they cut DNA. But what if we could write directly into the genome, inserting whatever we want, wherever we want, without ever making a single cut?

This isn't just a "wouldn't it be nice" daydream anymore. Researchers at the Arc Institute have discovered a new system that does exactly that. They're calling it "bridge recombination," and it might just be the biggest revolution in genetic engineering since CRISPR.

II.

To understand why this is such a big deal, we need to take a quick tour through the history of genetic manipulation.

In the late 1990s, we discovered RNA interference (RNAi). This was our first real taste of programmable biology. We could use short RNA sequences to target and shut down specific genes. It was like having a universal remote control for gene expression. Cool, right?

Then came CRISPR in the early 2010s. Suddenly, we could not just turn genes off, but edit them directly. It was like upgrading from a remote control to a basic text editor. We could cut out bad genes and paste in good ones. But there was always a catch: CRISPR works by cutting DNA, and cells don't always repair those cuts exactly the way we want them to.

Both of these systems were revolutionary, but they shared a common limitation: they were destructive. They worked by breaking things – either the RNA transcripts of genes (in the case of RNAi) or the DNA itself (in the case of CRISPR).

III.

Enter the bridge recombination system.

The researchers at Arc Institute, led by Dr. Patrick Hsu, were poking around in the genomes of bacteria, looking at transposable elements. These are sometimes called "jumping genes" because they can cut themselves out of one part of a genome and paste themselves into another.

They were particularly interested in a group called IS110 elements. These are about as minimalist as you can get while still being functional – just a gene for the enzyme that does the cutting and pasting, plus some mysterious flanking DNA segments.

What they found was surprising. When an IS110 element cuts itself out of a genome, those mysterious flanking segments join up to form an RNA molecule. This RNA folds into two loops, one that binds to the IS110 element itself, and another that binds to the target DNA where the element will insert itself.

This RNA – which they've dubbed "bridge RNA" – is the key to the whole system. It's like a set of instructions, telling the enzyme exactly where to insert the DNA and what DNA to insert.

IV.

Now, you might be thinking, "Okay, that's neat, but how is this different from CRISPR?" The key is in how the insertion happens.

CRISPR works by making a cut in the DNA and then relying on the cell's repair mechanisms to insert the new DNA. It's effective, but it's also a bit like performing surgery with a chainsaw. Sometimes you get exactly what you want, but often you end up with small errors or unwanted insertions or deletions.

The bridge recombination system, on the other hand, doesn't cut the DNA at all. It unzips a small section, inserts the new DNA, and zips it back up again. No broken DNA strands, no relying on error-prone repair mechanisms. It's precise in a way that CRISPR can only dream of.

But the real magic is in the programmability. Remember those two loops in the bridge RNA? They can be programmed to recognize any DNA sequence. This means you can tell the system to insert any piece of DNA into any location in the genome. It's like having a word processor for DNA.

V.

The implications of this are staggering. Here are just a few possibilities:

• Gene Therapy 2.0: Current gene therapy approaches often rely on somewhat random insertion of therapeutic genes. With bridge recombination, we could insert corrective genes exactly where they need to go, without risking disruption of other important genes.
• Synthetic Biology: Want to give an organism a completely new capability? Just design the gene and insert it precisely where you want it.
• Evolutionary Biology: We could insert reporter genes at specific locations across the genome, allowing us to watch evolution happen in real time.
• Agricultural Improvements: We could insert beneficial genes into crops with unprecedented precision, potentially revolutionizing our ability to create drought-resistant or nutrient-enhanced plants.
• Bioengineering: Imagine being able to design and build entire genetic circuits, inserting each component exactly where it needs to be for optimal function.

VI.

In the grand scheme of things, the discovery of bridge recombination feels like a pivotal moment. It's as if we've been trying to write the book of life with a typewriter, and someone just handed us a word processor.

The researchers at Arc Institute have opened a door to a new era of genome design. As with any breakthrough of this magnitude, it's hard to predict exactly where it will lead. But one thing is certain: the future of biology just got a lot more interesting.

As we stand on the brink of this new frontier, I'm reminded of a quote from Arthur C. Clarke: "Any sufficiently advanced technology is indistinguishable from magic." With bridge recombination, we're not just editing the genome anymore. We're writing it. And that, my friends, is pretty close to magic.

[CEEPS @CrecCeeps]

This week CEEPS members had the pleasure to participate to the Polk county Agri-Fest to talk about citrus production in Florida to 4th graders����🍋🐊 @uf @UFIFASCitrusREC @UFCitrusBugs #extension #outreach #floridacitrus

[Nian Wang @NWangUF]

The Wang lab at UF is hiring a postdoc and a senior scientist. Related publications by the Wang lab: Huang etal.2023. Nat Plants. doi: 10.1038/s41477-023-01520-y; Su etal. 2023. Nat Commun. 14:3957; and Ma etal. 2022 Nat Commun. 13:529. Expected Salary: $55,000-65,000. Please RT.

[CEEPS @CrecCeeps]

What an amazing day the CEEPS had with the kids from the lake Alfred elementary school!! We taught about soil sciences, entomology and pathology.
Thanks to all our grad student and postdocs for volunteering ! Amazing team work 🍊🦠🔬🐞🙂@UFIFASCitrusREC #UF #outreach

[Nian Wang @NWangUF]

I am thrilled to report a cool method for transgene-free plant genome editing in the T0 generation led by Drs. Xiaoen Huang and Hongge Jia. It is particularly useful for transgene-free genome editing of vegetatively propagated and perennial plant species. https://t.co/rLErQ6UMVf.

[Sarah Evanega @Sarah_Evanega]

In my recent @TEDx talk @Cornell I share some of the exciting #CRISPR apps that stand to have positive impact on us as a society and as individuals. It’s a little bit of science, a little bit of a reveal, and part personal story. #agbiotech #geneediting
https://t.co/JPUSD5reE8

[Nian Wang @NWangUF]

CRISPR Helps Scientists Develop Canker-resistant Citrus Lines in Less Than a Year https://t.co/IAgJt24vbb

[Nian Wang @NWangUF]

I am thrilled that our work is finally published and our transgene-free canker resistant citrus generated by Cas12a RNP has received regulatory approvals from APHIS and EPA! Thanks Hang for the persistence. Thanks our collaborators. It took us >5 years!
https://t.co/z7iHnKt2H4

[Nian Wang @NWangUF]

Dear colleagues, plant pathologists, early career scientists, students in plant pathology, please define the KEY challenges in plant pathology in the next decade by conducting the survey organized by Phytopathology and APS: https://t.co/sxbSyr4KjH. Please RT. @Phytopathology

[Nian Wang @NWangUF]

Our most exciting work so far. It took us more than 5 years to generate transgene-free canker-resistant Citrus. Thanks APHIS for the regulatory approval! Congrats to Hang and team! https://t.co/zn5zZuFr8D #bioRxiv. @UF_IFASResearch @IFAS_VP @UF_IFAS

[UF/IFAS @UF_IFAS]

Have you heard the news @UFCALS alumni? @UF was ranked the 4th best #AgriculturalScience university in the nation 🐊🚜 https://t.co/PMaBcPxkdT

[Xiaoen Huang @Sean4huang]

The final version of our paper is published today. We used ABE to generate disease-resistant citrus, CBE to generate transgene-free, herbicide-resistant citrus.
Base Editors for Citrus Gene Editing https://t.co/BSFlSVfWcr
@NWangUF @YuanchunW

[Javier Dalmendray @JDalmendray]

@hailingj1 @NWangUF Congrats!!!