Roman Graf

Antibody-lectin chimeras for glyco-immune checkpoint blockade - Nature Biotechnology Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.

Out now: We present antibody-lectin chimeras (AbLecs) as a molecular platform to target sugars, or glycans, for cancer immunotherapy.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
@mitkochinstitute.bsky.social @mitdeptofbe.bsky.social @mitcheme.bsky.social @stanford-chemh.bsky.social

Elucidating lipid nanoparticle properties and structure through biophysical analyses - Nature Biotechnology Guidance for optimizing lipid nanoparticle formulations is derived using sophisticated biophysical techniques.

Elucidating lipid nanoparticle properties and structure through biophysical analyses - @guptapenn.bsky.social
@pennengineering.bsky.social @pennmedicine.bsky.social go.nature.com/4oTt639

Jennifer Doudna startup launches with $82M to apply new CRISPR delivery technology to in vivo CAR-T Nobel laureate Jennifer Doudna's Azalea Therapeutics raises $82M to develop new CRISPR delivery system for in vivo CAR-T cell therapies targeting blood cancers.

Jennifer Doudna's latest startup, Azalea Therapeutics, launched with $82M. It's based on virus like particles developed by CEO Jenny Hamilton and a new CAR-T trick developed by UCSF's Justin Eyquem. Their goal? The ultimate CRISPR-based in vivo CAR-T. @endpts.com - endpoints.news/jennifer-dou...

Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy - Nature Biomedical Engineering A computational method designs receptors called T-SenSERs, which have predictable signalling responses to tumour microenvironment soluble factors and can be co-expressed with conventional CARs in T ce...

💡 This article offers a #computational method to create #synthetic receptors that help engineered T cells respond more effectively to #tumors.

Read the paper published by J. A. Rath et al., in @natbiomedeng.nature.com
🔗 www.nature.com/articles/s41...

Integrated epigenetic and genetic programming of primary human T cells - Nature Biotechnology Multiplexed editing in primary human T cells generates enhanced immune cell therapies.

Integrated epigenetic and genetic programming of primary human T cells - @gladstoneinst.bsky.social @ucsanfrancisco.bsky.social @j-eyquem.bsky.social @marsonlab.bsky.social go.nature.com/3WOJJAJ

In vivo chimeric antigen receptor (CAR)-T cell therapy - Nature Reviews Drug Discovery In vivo chimeric antigen receptor (CAR)-T cell engineering uses targeted delivery systems to generate CAR-T cells directly in patients, bypassing ex vivo manufacturing. This Review examines emerging viral and lipid nanoparticle platforms, early clinical proof of concept and potential applications beyond cancer.

For readers interested in finding out more about in vivo CAR-T therapies such as those at the centre of the $1.5 billion acquisition of Orbital Therapeutics by Bristol Myers Squibb today, here's a comprehensive review
rdcu.be/eKnwV
nature.com/articles/s41...

Systematic discovery of CRISPR-boosted CAR T cell immunotherapies - Nature CELLFIE, a CRISPR platform for optimizing cell-based immunotherapies, identifies gene knockouts that enhance CAR T cell efficacy using in vitro and in vivo screens.

CAR T cells showcase the enormous potential of cell therapies, but often fail due to lack of evolutionary optimization. Today in @nature.com , we use #CELLFIE to engineer cell therapies at scale and share the largest resource of CRISPR screens in CAR T cells. www.nature.com/articles/s41...

📢 New in #Nature!

Researchers led by Dr. Chris at Stanford have leveraged synthetic #CytokineReceptor engineering to successfully rewire #TCell fate decisions and amplify anti-cancer immunity.

📗: https://go.nature.com/4n6F6gQ
🔊: https://bit.ly/4mYJIWy

A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2 - Nature Biotechnology A screen for protein degraders discovers hits by imaging cell survival.

A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2 go.nature.com/4mTBGhr

Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

www.nature.com/articles/s41...

In case of a successful application for the Venture Science PhD program and a Helmholtz host laboratory where the boss is a TUM professor, would it be possible to also enrol at TUM for a PhD with that scholarship? So basically getting a double degree from TUM + Woolf University

Targeted delivery of diverse biomolecules with engineered bacterial nanosyringes - Nature Biotechnology Ribonucleoproteins, nucleic acids and proteins are delivered into target cell types with nanosyringes.

Targeted delivery of diverse biomolecules with engineered bacterial nanosyringes - @zhangf.bsky.social go.nature.com/46OFcoj

PANCS-Binders (phage-assisted noncontinuous selection of protein binders) screens multiple high-diversity protein libraries against a panel of dozens of targets for high-throughput binder discovery. @chembiobryan.bsky.social @mstyles-chembiol.bsky.social

www.nature.com/articles/s41...

Design of highly functional genome editors by modelling CRISPR–Cas sequences - Nature Gene editors designed using artificial intelligence can undertake precision editing of the human genome.

Nature research paper: Design of highly functional genome editors by modelling CRISPR–Cas sequences

go.nature.com/3UAYBBB

Extracellular exosomal RNAs are glyco-modified - Nature Cell Biology Sharma, Jiao and colleagues report glycosylation of small RNAs within exosomes and propose a glycosylation-dependent mechanism for RNA targeting into exosomes, which may influence intercellular commun...

🍹Sharma, Jiao et al. report glycosylation of small RNAs within #exosomes and propose a glycosylation-dependent mechanism for #RNA targeting into exosomes, which may influence intercellular communication and RNA stability in the extracellular environment.
👉https://rdcu.be/eykKY
bit.ly/455vyuP

I am super excited to announce that I will be starting my lab at the Department of Pharmacology of the University of Zurich in Switzerland next year!

An alternate receptor for adeno-associated viruses Dhungel et al. report an alternate receptor for AAV (AAVR2, carboxypeptidase D), which is distinct from the multi-serotype AAV receptor (AAVR). This study provides insights into AAV biology and clinic...

An alternative receptor enhances AAV transduction in vivo, offering the potential to reduce dose-related toxicities while maintaining efficacy in AAV-mediated gene therapy. www.cell.com/cell/fulltex... #NBThighlight

Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery - Nature A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

Nature research paper: Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery

https://go.nature.com/3TRMdNd

Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes | NEJM Zimislecel is an allogeneic stem cell–derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. We conducted a phase 1–2 study of zimisle...

What an amazing time to be a biomedical scientist.

www.nejm.org/doi/abs/10.1...

In vivo CAR T cell generation to treat cancer and autoimmune disease Chimeric antigen receptor (CAR) T cell therapies have transformed treatment of B cell malignancies. However, their broader application is limited by complex manufacturing processes and the necessity f...

CD8-targeted lipid nanoparticles carrying anti-CD19 CAR mRNA were developed to generate CAR-T cells directly in vivo, demonstrating effective B cell depletion for potential treatment of B cell malignancies and autoimmune diseases. www.science.org/doi/10.1126/... #NBThighlight

Excited to unveil Boltz-2, our new model capable not only of predicting structures but also binding affinities! Boltz-2 is the first AI model to approach the performance of FEP simulations while being more than 1000x faster! All open-sourced under MIT license! A thread… 🤗🚀

Synthetic biology could enable new types of programmable therapeutics. Our new preprint introduces synthetic protein circuits that selectively trigger cell death in Ras-mutant cancer cells, with interesting advantages compared to existing approaches.
www.biorxiv.org/content/10.1...

Reprogramming site-specific retrotransposon activity to new DNA sites - Nature A study of retrotransposon activity repurposes a retroelement called R2Tocc to create a programmable system called STITCHR that enables diverse genome edits including efficient, scarless large pa...

The gene editing tool STITCHR contains an R2 retrotransposon fused to a CRISPR–Cas9 nickase to install diverse edits, including multi-kilobase insertions, in vitro. www.nature.com/articles/s41... #NBTHighlight

Evolution-guided protein design of IscB for persistent epigenome editing in vivo - Nature Biotechnology A combination of engineering approaches is used to improve the function of IscB for a variety of editing activities in vivo.

Evolution-guided protein design of IscB for persistent epigenome editing in vivo - @zhangf.bsky.social @broadinstitute.org @hhmi.org go.nature.com/44XVBph

1/10 Today in @science.org in collaboration with
the Liu group we report the development of a laboratory-evolved CRISPR-associated transposase (evoCAST) that supports therapeutically relevant levels of RNA-programmable gene insertion in human cells. drive.google.com/file/d/1I-Ub...

Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins - Nature Biotechnology Biomacromolecules are delivered into cells using nanoparticles made of elastin and endosomal escape sequences.

Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins - @bidmcreseach.bsky.social go.nature.com/4mxazJw

Implantation of engineered adipocytes suppresses tumor progression in cancer models - Nature Biotechnology Adipose manipulation transplantation can reduce tumor growth and proliferation in vitro and in mouse models.

Tumors need a lot of nutrients to grow. By engineering and implanting fat cells to outcompete cancers for nutrients we can suppress them. Novel cancer therapy called Adipose Manipulation Transplantation (AMT). AMAZING work led by and dedicated to Hai Nguyen.
www.nature.com/articles/s41...

SEED-Selection enables high-efficiency enrichment of primary T cells edited at multiple loci - Nature Biotechnology Primary T cells with multiple genetic modifications are rapidly isolated by negative selection.

Excited to share our latest work, now out in
@NatureBiotech
! We introduce SEED-Selection, a powerful method that enables high-efficiency enrichment of T cells edited at multiple loci in a single step 🧵👇

www.nature.com/articles/s41...

Engineered nucleocytosolic vehicles for loading of programmable editors Engineered nucleocytosolic vehicles for loading of programmable editors (ENVLPE) with enhanced CRISPR ribonucleoprotein (RNP) loading and stabilization enable the efficient delivery of gene-editing ef...

www.cell.com/cell/fulltex...
ENVLPE, our system for VLP-based delivery of gene editors, is now published in @cellcellpress.bsky.social. We showed efficient delivery of base- and prime-editors in primary T cells & in vivo retinal models. All core constructs are available from @addgene.bsky.social.