Feng Zhang
@zhangf
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Engineer and molecular biologist. Curious about the world and optimistic to make it better.
Joined April 2015
We are excited to share STOPCovid, an inexpensive, one-step, & sensitive #COVID-19 detection protocol developed with @omarabudayyeh & @jgooten. This revamped assay was streamlined with the future goal of developing an in-home test for COVID-19. 1/X
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CRISPR technologies are powerful gene editing tools because they are programmable. We are excited to describe 3 new programmable systems, IscB, IsrB, and TnpB, some of the most abundant genes on the planet, with potential for gene editing. @ScienceMagazine
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We are really excited to share our work on a new modular RNA delivery technology called SEND, built from endogenous components found in the mammalian genome. @ScienceMagazine
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Our genomes are littered with *junk* DNA known as LINE retrotransposons, which are powerful enzymes that can insert DNA into the genome. We are excited to report the structure of the LINE family member R2 and ways to engineer it for programmable gene insertion. Congratulations to.
How do LINE family retrotransposons jump around?.Can we reprogram retrotransposons?.What does this have to do with Rum and Raisin?.Answers here and below!
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We are excited to report the discovery of TIGRs, a widely-occurring RNA-guided system found in bacteria and their viruses. TIGRs consist of a peculiar repeat region which is transcribed into RNA and processed into multiple guide RNAs to direct TIGR-associated proteins to their.
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Extracting RNA from patient swab samples has been a bottleneck for #COVID19 #coronavirus testing. See here for a simple 5-min protocol from swab to RT-qPCR.
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Today we are sharing a research protocol for SHERLOCK-based COVID-19 #coronavirus detection, and hope it will help others who are working to combat the outbreak. We will continue to update this as we make further progress:
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Thrilled to announce our latest exploration of CRISPR! By developing an advanced algorithm, we’ve analyzed 8 terabases of microbial data, leading to the discovery of over 200 novel CRISPR systems. Kudos to @altaetran and @soumya_kannan12 for their exceptional work! Details in the.
Our latest work exploring ultra rare CRISPR systems with new big data algorithms has been published by @ScienceMagazine! @zhangf @soumya_kannan12. This thread will unwrap how we found needles in a haystack of metagenomes. Let's dive in! (1/8)
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CRISPR systems are quite diverse, including some, like CRISPR-Cas13, which target RNA. @soumya_kannan12 & @altaetran found tiny versions of Cas13b (Cas13bt) that can be used to create RNA editors small enough to fit into a single AAV for in vivo delivery.
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Did you know there are lots of similarities between the innate immune systems of animals/plants and the phage defense systems in bacteria? Check out our new study by the amazing trio Alex (Linyi) Gao, @maxewilkinson, and @thestrecker. Congratulations!
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Nature is amazing! Congratulations to @maxewilkinson and team on a beautiful study revealing a clever way that bacteria defend against viruses. Check out Max’s posts for more detail!.
My favourite discovery ever has just come online. Can I please tell you about some seriously wacky molecular biology? The story starts with a reverse transcriptase that SOMEHOW defends bacteria from viruses. (👇 I recommend sound ON for the video 🎹).1/
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#CRISPR2022 begins today! Excited for all of the great discussions and learnings this week.
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I’m so incredibly excited and inspired to see @eric_lander (and @FrancesArnold and @maria_zuber) shaping the scientific future of our country in their new roles in @JoeBiden's science team! It gives me even more hope for our future!.
This team will help our administration confront some of the biggest crises and challenges of our time, from climate change and the impact of technology on society to pandemics, racial inequity, and the current historic economic downturn.
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Excited to share STOPCovid.v2 for #COVID19 diagnostics. Grateful for collaborators who helped make this happen! @JuliaJoung @LadhaAlim @jgooten @omarabudayyeh KeithJerome @GreningerLab NamGyunKim @UWVirology @AnnWoolleyMD DebHung @brucedwalkermd @DrJLi.
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Congratulations and thank you to @rahulkdhanda and the entire @Sherlock_Bio team for achieving this huge milestone for the #CRISPR field. Proud of all teams working hard to fight this pandemic!.
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A beautiful bridging (pun intended) of basic science and technology!.
Just shared at @KeystoneSymp a new @ArcInstitute discovery of the bridge RNA recombinase mechanism: a new class of natural RNA-guided systems that retains the key property of programmability from RNAi and CRISPR while enabling large-scale genome design beyond RNA and DNA cuts
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We are pleased to share a follow-up story to our study of CRISPR-associated transposases (CAST) led by Makoto Saito, @LadhaAlim, @thestrecker, and Guilhem Faure: 1/5.
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Inspiring visit at the @arcinstitute today with @pdhsu & @SKonermann. Thoughtful vision, exciting science, and amazing potential.
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Happy 2025=1^3+2^3+3^3+4^3+5^3+6^3+7^3+8^3+9^3 and many new discoveries!
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1/N Excited to unveil Tn7 transposon target selectors study! What defines the target specificity of Tn7-like Tn to spread to MGEs & integrate back into bacterial genomes? #transposons #Tn7 #CAST
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This is really exciting!.
Therapeutic mRNA for heart failure?!. Our own Joel Rurik (@DevBioAcademic) teamed up with @WeissmanLab to make CAR T cells entirely in the body to treat heart disease. Published today on the cover of Science!.. @CAMBUpenn @PennBGS @ScienceMagazine. 1/6.
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Congratulations to all of the graduates during this commencement season! Wishing you all a creative and fulfilling future!. "What you follow with your heart will indeed come back to make your life much richer."
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Excited to announce HowWeFeel, an open platform for helping us fight the pandemic. Grateful for collaboration w/ @8en @XihongLin @kinggary @ophirshalem @GreeneScientist @bitdrift @rpjb and many other great colleagues. Visit #COVID19Pandemic #coronavirus
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Had a blast diving deep into discussions on leadership, community, culture, and scientific vision at the @broadinstitute's annual faculty retreat. Also, that engineering challenge was a fun twist! 🧪
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Congratulations @nevillesanjana! Elegant and very timely!.
As promised, here’s an overview of our study to find host factors required for SARS-CoV-2 infection in human cells. We use a genome-wide CRISPR screen to identify genes (& key mechanisms) that might be therapeutically targetable to prevent viral infection.
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Registrations are open for #CRISPR2022, at @MIT 06/12/22-06/16/22. Featuring keynote by @eugene_koonin and many other exciting speakers. Register today!
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Enabling testing at home and in low-resource settings requires that we can’t be reliant on complex instrumentation. #STOPCovid can be used with a sous-vide cooker (<$40). 3/X
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Excited to see our team’s work on Fanzor now published in @CellCellPress! Amazing effort by @Peiyu_Xu_ and the entire team in uncovering the structural diversity and DNA cutting mechanisms of Fanzor. Proud of everyone involved! Onward to more discoveries. 🚀.
Excited to share that our latest work on Fanzor is now online in @CellCellPress ! By analyzing structures from different species, we’ve uncovered the structural diversity and how they cut DNA. Huge thanks to Feng @zhangf , Makoto, and all collaborators!
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Congratulations to @rumya_r @mircoscopy @DStrebinger @blake_lash @cyrusbiotech and colleagues on an exciting study combining AI and protein engineering to minimize the immunogenicity of Cas9 and Cas12a nucleases. These approaches have the potential to improve the safety and.
1/ Thrilled to share an advancement in gene therapy from my PhD in @NatureComms! We've developed a new approach to reduce immune responses while maintaining efficiency—paving the way for safer, more effective therapies. Big thanks to @zhangf & @mircoscopy!
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8/ This was led by @altaetran & @soumya_kannan12, and with EDemircioglu, @rachel_oshiro, SNety, @GCACTAATTGAGAAC, MDlakic, @Ivan_Bilinski, KMakarova, RMacrae, @eugene_koonin. We are excited to continue exploring nature’s diversity and advancing programmable therapeutics.
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Congratulations @JuliaJoung and team on a beautiful study utilizing genome-scale CRISPR activation screening to discover drivers for resistance to T-cell killing, with implications for immunotherapy for cancer.
Excited to share the latest work from my PhD! We performed the first CRISPR activation screen to identify genes that drive solid tumor resistance to T cell-mediated cytotoxicity. A thread 1/X.
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We have some LwCas13 protein to share for research purposes with thanks to @NEBiolabs for providing a batch for us to share. Please fill out the form to request some for your project. Limited availability.
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We have an open position for a 🧬 Molecular Biologist/Biochemist/Structural Biologist. We look forward to hearing from you!.
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Thank you @eugene_koonin for your science and even more importantly for your humanity. I’m so honored to have you as my colleague and friend.
Dr. Eugene Koonin, a member of National Academy of Sciences of the USA and of Russian Academy of Sciences, wrote this open letter today to the President of RAS Prof. Alexander Sergeev demanding that RAS issues an official anti-war statement in 48h, otherwise he resigns from RAS.
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8/ Last but not least, this was led by postdoc @michael_s_segel and grad student @blake_lash, and great collaborators JSong @catherinecliu (not pic'd @xinjin @LadhaAlim SLMekhedov RMacrae @eugene_koonin). We are excited to continue developing SEND into a therapy to help patients.
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Congratulations to the 2024 class of @Regeneron #sciencetalentsearch finalists - inspirations and hopes for the future. Keep persevering, keep shining! @Society4Science
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We are making a limited number of research-use-only #STOPCovid reagents available for free to the research community. Updates to the protocol and data will be added to our website Reagent request form: 6/6
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#STOPCovid requires no sample extraction, can be performed using a single mastermix, and uses a paper strip to display results. #STOPCovid can detect down to 100 copies of SARS-Cov-2 RNA from patient samples. 2/X
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1/ Inspired by the machinery used by endosymbiotic bacteria to deliver protein payloads to their host animals’ cells, we sought to engineer these systems, called contractile injection systems (CISs), for delivery to human cells.
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Congratulations @soumya_kannan12 and @altaetran!.
The February issue is live Our cover features a rendering of the predicted structure of an RNA editor based on the compact Cas13bt enzyme presented by Kannan et al.
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Please join us in Cambridge, MA for the 7th annual Genome Engineering Workshop May 19 & 20th, 2019. The theme this year is CRISPR in vivo. Look forward to seeing you there!.
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Super proud of the #STOPCovid team, @JuliaJoung, @LadhaAlim, @omarabudayyeh, @jgooten, MSegel, MSaito, RMacrae, and EBlackwell who have worked tirelessly for achieving this advance. We are charging forward to develop this into a turn-key solution for at-home testing. 4/X
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Congratulations to @thestrecker, Esra Dimircioglu, @_David_Li, @GuilhemFaure, and co on another tour de force study in @ScienceMagazine! Elegant biology & beautiful integration of diverse techniques. Still so much more to explore! See David’s tweets for details.
Excited to see our work in the ZLab @zhangf on the protease Csx29 out! Led by the amazing @thestrecker with beautiful structures driven by Esra Dimircioglu, we show that Csx29 complexed with CRISPR protein Cas7-11 (aka gRAMP) is an RNA-triggered protease.
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Check out the resource provided by Mammoth. Glad that scientists are working together and sharing openly. #coronavirus
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5/ IscB can be engineered to edit genomes in human cells. The small size of IscB (~30% the size of Cas9) makes it an ideal candidate for in vivo genome editing technologies.
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Many “thank you” to my entire lab and lab alum for putting together a phenomenal GE7.0 workshop. Thank you to all of the participants for lots of great discussions, brainstorms, and forging of new collaborations. See you next year! #genomeengineering2019
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1/x In exploring the evolution of Cas9, we identified Fanzor (Fz) as a putative RNA-guided nuclease while studying IscB, IsrB, and TnpB–collectively called OMEGA systems–in collaboration with Eugene Koonin’s group. Here, we expand our analysis of the diversity of Fz proteins,
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1/ Delivery of nucleic acid therapies to cells remains a bottleneck for gene therapy. We wanted to develop a modular delivery system that would be safe and cell-type type specific, avoiding the immunogenicity of common viral vectors.
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Happy 60th @eric_lander! Thank you for the family you have created for us and for continuing to be our inspiration!
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Congratulations @SKonermann and @pdhsu on this exciting adventure!.
I am incredibly excited to announce after nearly two years in the making. @arcinstitute is a new, nonprofit research institute launched in collaboration with @Stanford, @UCSF, and @UCBerkeley that will focus on complex diseases.
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1/ We were exploring Cas9 diversity when we found IscB, a transposon-encoded protein that shares nuclease domains with Cas9. However, unlike Cas9, no RNA or CRISPR components are known to interact with it, making its function a mystery.
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There’s likely so much more physics that still await our discovery.
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2/ Using both computational and experimental approaches, we found IscB associates with a new, diverse class of large structured non-coding RNAs, termed omegaRNAs.
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Congratulations @JuliaJoung on completing this heroic project and leading an amazing team!.
Thrilled to share my primary PhD work: a Transcription Factor Atlas for understanding gene regulation and cell engineering @CellCellPress. We created a comprehensive TF ORF library and applied it to profile resulting expression changes. A thread 1/X
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9/x This work was led by postdocs Makoto Saito and Peiyu Xu in collaboration with @GuilhemFaure , S. Maguire, @soumya_kannan12, @altaetran, S. Vo & A. Desimone. Congratulations on a beautiful and comprehensive study!.
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8/x Fz shares structural similarities with TnpB and Cas12, but the interaction between the ωRNA and the catalytic domains of Fz is notably more extensive, suggesting that the ωRNA might play a role in the catalytic reactions involving Fz.
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6/ To our surprise, we also functional IscB genes in the eukaryotic cells, in the chloroplast of green algae I. tetrasporus.
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7/ Beyond IscB, we uncovered additional classes of OMEGA systems, TnpB and IsrB, that also function as programmable RNA-guided endonucleases and nickases, respectively.
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Last but not least, huge thanks to our supporters, in particular @HHMI, @McGovernMIT, @broadinstitute, @NIH, @open_phil, Mathers Fdn, J.&P. Poitras, M.&L.&E.Schwartz, and @NEBiolabs, @Quintara_Bio, @Synthego, & MileniaBiotec for their big help. 5/X.
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5/ Using #AlphaFold to model Pvc13, we predicted which part of Pvc13 contacts target cells and used this information as a guide to insert binding domains specific to human cells into Pvc13. We confirmed these PVC variants bound to and delivered cargo to the intended target cells.
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4/ Using phylogenetic analysis and enabled by collaborator (@GCACTAATTGAGAAC, MDlakic, @Ivan_Bilinski) samples from Yellowstone Lake, we identified a new Cas9 subtype II-D and show that CRISPR-Cas9 likely evolved from ancestral OMEGA systems.
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7/ This work was led by graduate student Joe Kreitz (@kreitz_joseph) with collaboration from MFriedrich (@mircoscopy), AGuru (@Akash_Guru_), BLash (@blake_lash), and MSaito.
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6/ We took a similar structure-guided approach to target neurons in the mouse brain, showing in vivo delivery of a cargo protein specifically to neurons. We are continuing to expand the targeting and packaging abilities of PVCs and test them in vivo.
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Congratulations @Society4Science 2019 #intelisef finalists! You are our inspiration and our future!
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Congratulations @VivianGradinaru and @TheHongLab! Excited to see your creativity and impact getting recognized. Viv, we should revisit those old ideas again!.
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We are indebted to have @JKeithJoung kick off GE7.0 with an exciting keynote on latest advances in genome editing.
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7/ SEND can be used to deliver different payloads including Cas9 and guide RNAs to human cells.
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3/ Naturally occurring omegaRNAs contain a guide sequence that directs IscB to its target DNA. This guide can be reprogrammed to target IscB to DNA sequences.
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2/ Given cool findings by Vivian Budnik/Travis Thomson and @jasonsynaptic showing the retrotransposon-derived protein ARC forms capsids and transfers mRNA between cells, we collaborated with Koonin lab to identify other retroelement-derived proteins that might form capsids.
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7/x Finally, to gain insight into the mechanism of Fz and guide future development, we used cryo-EM to resolve the structure of SpuFz1 in complex with ωRNA and target DNA at 2.7 Å.
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What’s next?.- Understanding TIGR’s natural function—Defense system? Genome organizer? A new function yet to be discovered?.- Engineering TIGR for precision genome editing. - Exploring relationships with box C/D snoRNPs and IS110 transposases and uncovering more Nop-based
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Most RNA-guided systems are found by searching for conserved nuclease domains. We took a different approach, starting from Cas9 REC domains using structural mining, Iterative searches, and LLM-based clustering.
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Endymion Wilkinson who taught me Chinese history in college just released the 6th edition of the “Chinese History” manual. It is inspiring to see how a diplomat’s passion project turned into a cornerstone resource for Sinology research.
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2/x Fz1 and Fz2 share similar domain architecture and catalytic residues with the OMEGA effector TnpB and the CRISPR effector Cas12, and our analysis suggests TnpB evolved into both prokaryotic Cas12 and eukaryotic Fz.
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2/ We focused on the Photorhabdus virulence cassette (PVC), a type of CIS that is secreted by Photorhabdus and known to infect insect and mouse cells. We reconstituted PVCs in E. coli and confirmed they could attach to insect cells, their native target.
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This work was led by the phenomenal team of @GuilhemFaure, Makoto Saito, @maxewilkinson, in collaboration with Natalia Quinones-Olvera, @Peiyu_Xu_, @FlamShepherd, Stephanie Kim, @NishRReddy, Shiyou Zhu, @LiliaEvgeniou, @eugene_koonin, Rhiannon Macrae.
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3/ We then explored if we could replace the endogenous cargo protein with a protein of interest. To do this, we introduced a packaging signal on a cargo protein (GFP, Cre, or ZFN), confirmed it was loaded by the PVC, and showed it functioned in recipient insect cells.
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Unlike CRISPR, TIGR is PAM-free, allowing broader targeting. We demonstrated TasR-mediated genome editing in human cells, opening the door for TIGR-based tools, including RNA-guided DNA notifications, base editing, etc.
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3/x Based on this, we predicted Fz is also an RNA-guided DNA endonuclease. To test this, we first performed RNA pull-downs with Fz1 and Fz2 and found these proteins bind to the non-coding RNA found in Fz loci, confirming this region encodes an ωRNA.
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3/ A number of retroelement-derived proteins form virus-like particles and are secreted when expressed in HEK cells, including PEG10.
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4/ We focused on PEG10 because it self-assembled into capsids, was efficiently secreted as extracellular vesicles, bound its own RNA in the UTRs, and carried its own mRNA out of the cell.
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