Alex Cornean

Discovery and characterisation of gene by environment and epistatic genetic effects in a vertebrate model Phenotypic variation arises from the interplay between genetic and environmental factors. However, disentangling these interactions for complex traits remains challenging in observational cohorts such...

New pre-print klaxon: "Discovery and characterisation of gene by environment and epistatic genetic effects in a vertebrate model" led by the excellent Bettina Welz + @saulpierotti.bsky.social from @wittbrodtlab.bsky.social, Felix Loosli, Kiyoshi Naruse and my own lab www.biorxiv.org/content/10.1...

3️⃣ SPLICER: a highly efficient base editing toolbox that enables in vivo therapeutic exon skipping.
4️⃣ Cytosine base editors with increased PAM and deaminase motif flexibility for gene editing in zebrafish.

Notable mentions:
1️⃣ Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.
2️⃣ Engineered IscB-ωRNA system with improved base editing efficiency for disease correction via single AAV delivery in mice.

✨ A benchmarked, high-efficiency prime editing platform for multiplexed dropout screening.
✨ Multimodal scanning of genetic variants with base and prime editing.
✨ Directed evolution of engineered virus-like particles with improved production and transduction efficiencies.

✨ In vivo Treatment of a Severe Vascular Disease via a Bespoke CRISPR-Cas9 Base Editor. @bkleinstiver.bsky.social
✨ Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia. @bkleinstiver.bsky.social

Spotlights include:
✨Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases.
✨ PAM-flexible adenine base editing rescues hearing loss in a humanized MPZL2 mouse model harboring an East Asian founder mutation.

Once again, so much happened across genome editing and gene therapy, and I’d like to highlight four topics:
🔎 CRISPR, HDR and deletions
🔎 Disease modelling and gene therapy
🔎 Screens
🔎 Delivery

So these are, to me, the most exciting genome editing papers published in (or around) November! I promise the December highlight will be out by the second week of January!

I’ve just published a new Substack Blog Post with my roundup of standout papers from the past month. These publications feature ingenious strategies to tackle genome engineering and gene therapy challenges. tinyurl.com/alexdataharm...

3) BindCraft: one-shot design of functional protein binders. @martinpacesa.bsky.social
4) Rad51DBD-incorporated base editors improving zebrafish genome editing precision.

4) High-fidelity PAM-less base editing to treat chronic granulomatous disease. @bkleinstiver.bsky.social

Notable mentions:
1) Editing homologous globin genes with a nickase-deficient base editor to prevent large deletions.
2) Extended pegRNAs enhancing prime editing efficiency.

Spotlights include:
1) Packaged delivery of CRISPR-Cas9 RNPs to accelerate editing.
2) Lipid nanoparticle delivery enabling stable CRISPR-Cas9 lung and liver editing.
3) Rapid synthesis of chemically modified pegRNAs for prime editing.

2) Transformative splint ligation methods for scalable, cost-effective synthesis of (e)pegRNAs, enabling efficient RNA and RNP delivery.
3)Safe, precise ex vivo editing with PAM-less adenine base editors paired with high-fidelity variants and robust off-target analysis.

It was an incredibly productive month for our field, packed with innovations worth diving into. This month’s themes span breakthroughs in genome editing:
1) Fine-tuned investigation of RNP-based Cas9 editing using EDVs and in vivo editing via RNP-LNPs with engineered iGeoCas9 variants.

As my first post here, I thought I'd highlight a post I made on LinkedIn a few weeks ago, where I highlighted October's advances in Genome engineering and Gene therapy research in a substack post: tinyurl.com/GE-GT-10-2024