Alex Cornean
@alexdataharmony.bsky.social
Co-founder at DataHarmony | Genome engineer
Building a data co-pilot for Life Science research.
Previously: Subgroup leader Gene editing and gene therapy Freichel lab, Heidelberg University Hospital
PhD: Wittbrodt lab, @cosheidelberg.bsky.social
Building a data co-pilot for Life Science research.
Previously: Subgroup leader Gene editing and gene therapy Freichel lab, Heidelberg University Hospital
PhD: Wittbrodt lab, @cosheidelberg.bsky.social
Note: CMV and EF1α ABE9-SpRY constructs are coming to Addgene soon.
Thanks to everyone involved. Curious to hear your feedback here.
Thanks to everyone involved. Curious to hear your feedback here.
October 8, 2025 at 11:59 AM
Note: CMV and EF1α ABE9-SpRY constructs are coming to Addgene soon.
Thanks to everyone involved. Curious to hear your feedback here.
Thanks to everyone involved. Curious to hear your feedback here.
Why this matters:
Precision is essential when mutating a gene to study its function in health or disease. Therefore, our ABE9-SpRY approach is particularly relevant for those who require rapid disease modelling with accuracy and variant interpretation for A-to-G changes that lack NGG PAMs.
Precision is essential when mutating a gene to study its function in health or disease. Therefore, our ABE9-SpRY approach is particularly relevant for those who require rapid disease modelling with accuracy and variant interpretation for A-to-G changes that lack NGG PAMs.
October 8, 2025 at 11:59 AM
Why this matters:
Precision is essential when mutating a gene to study its function in health or disease. Therefore, our ABE9-SpRY approach is particularly relevant for those who require rapid disease modelling with accuracy and variant interpretation for A-to-G changes that lack NGG PAMs.
Precision is essential when mutating a gene to study its function in health or disease. Therefore, our ABE9-SpRY approach is particularly relevant for those who require rapid disease modelling with accuracy and variant interpretation for A-to-G changes that lack NGG PAMs.
6. In hiPSCs at the human orthologue (TPC1 p.I485T), ABE9-SpRY again showed higher precise, bystander-free editing than ABE8e-SpRY.
October 8, 2025 at 11:59 AM
6. In hiPSCs at the human orthologue (TPC1 p.I485T), ABE9-SpRY again showed higher precise, bystander-free editing than ABE8e-SpRY.
5. In individual injections, ABE9-SpRY installed Tpc1 p.I486T without bystanders at a median of 26% (up to 81%) and Trpm4 p.L903P at 21% (up to 96%); and we achieved F1 germline transmission.
October 8, 2025 at 11:59 AM
5. In individual injections, ABE9-SpRY installed Tpc1 p.I486T without bystanders at a median of 26% (up to 81%) and Trpm4 p.L903P at 21% (up to 96%); and we achieved F1 germline transmission.
3. ABE8e-SpRY yielded a very high average editing rate (52.6–99.8%) but more bystanders. ABE9-SpRY yielded higher precision and product purity at 3 of 4 sites.
4. DNA-dependent and DNA-independent off-target editing dropped substantially with ABE9-SpRY.
4. DNA-dependent and DNA-independent off-target editing dropped substantially with ABE9-SpRY.
October 8, 2025 at 11:59 AM
3. ABE8e-SpRY yielded a very high average editing rate (52.6–99.8%) but more bystanders. ABE9-SpRY yielded higher precision and product purity at 3 of 4 sites.
4. DNA-dependent and DNA-independent off-target editing dropped substantially with ABE9-SpRY.
4. DNA-dependent and DNA-independent off-target editing dropped substantially with ABE9-SpRY.
Key results:
1. N2a assays were a decent but conservative proxy for embryo editing.
2. Head-to-head screens with pooled guides at four sites: ABE9-SpRY vs ABE8e-SpRY worked great and reduced mouse usage in the first pass.
1. N2a assays were a decent but conservative proxy for embryo editing.
2. Head-to-head screens with pooled guides at four sites: ABE9-SpRY vs ABE8e-SpRY worked great and reduced mouse usage in the first pass.
October 8, 2025 at 11:59 AM
Key results:
1. N2a assays were a decent but conservative proxy for embryo editing.
2. Head-to-head screens with pooled guides at four sites: ABE9-SpRY vs ABE8e-SpRY worked great and reduced mouse usage in the first pass.
1. N2a assays were a decent but conservative proxy for embryo editing.
2. Head-to-head screens with pooled guides at four sites: ABE9-SpRY vs ABE8e-SpRY worked great and reduced mouse usage in the first pass.
The experimental work was primarily carried out by Jun Kai during his master’s thesis with me, with significant support from Sayari, Vanessa, Beate, Sascha, and Frank.
October 8, 2025 at 11:59 AM
The experimental work was primarily carried out by Jun Kai during his master’s thesis with me, with significant support from Sayari, Vanessa, Beate, Sascha, and Frank.
Our idea:
Pair the precision of the ABE9 TadA deaminase with the broad-target “PAM-less” SpRY nickase, which prefers NRN PAMs and can also recognise NYN sites.
Pair the precision of the ABE9 TadA deaminase with the broad-target “PAM-less” SpRY nickase, which prefers NRN PAMs and can also recognise NYN sites.
October 8, 2025 at 11:59 AM
Our idea:
Pair the precision of the ABE9 TadA deaminase with the broad-target “PAM-less” SpRY nickase, which prefers NRN PAMs and can also recognise NYN sites.
Pair the precision of the ABE9 TadA deaminase with the broad-target “PAM-less” SpRY nickase, which prefers NRN PAMs and can also recognise NYN sites.
Most targets were A-to-G, so adenine base editors were a good fit. The problems: multiple adenines cause bystander edits, and many sites lack NGG PAMs.
October 8, 2025 at 11:59 AM
Most targets were A-to-G, so adenine base editors were a good fit. The problems: multiple adenines cause bystander edits, and many sites lack NGG PAMs.
Why we did this:
We needed many mouse lines with single-base changes, fast. HDR with long biotinylated donors or ssODNs is effective, but throughput and yield are limited.
We needed many mouse lines with single-base changes, fast. HDR with long biotinylated donors or ssODNs is effective, but throughput and yield are limited.
October 8, 2025 at 11:59 AM
Why we did this:
We needed many mouse lines with single-base changes, fast. HDR with long biotinylated donors or ssODNs is effective, but throughput and yield are limited.
We needed many mouse lines with single-base changes, fast. HDR with long biotinylated donors or ssODNs is effective, but throughput and yield are limited.
In plain English: we built a more precise “single-letter” DNA editor and used it to make disease-relevant mouse and human cell models with far fewer side effects. That means faster, cleaner paths to studying disease.
October 8, 2025 at 11:59 AM
In plain English: we built a more precise “single-letter” DNA editor and used it to make disease-relevant mouse and human cell models with far fewer side effects. That means faster, cleaner paths to studying disease.
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.
4️⃣ Cytosine base editors with increased PAM and deaminase motif flexibility for gene editing in zebrafish.
December 28, 2024 at 1:55 AM
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.
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.
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.
December 28, 2024 at 1:55 AM
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.
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.
✨ Multimodal scanning of genetic variants with base and prime editing.
✨ Directed evolution of engineered virus-like particles with improved production and transduction efficiencies.
December 28, 2024 at 1:55 AM
✨ 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.
✨ 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
✨ Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia. @bkleinstiver.bsky.social
December 28, 2024 at 1:55 AM
✨ 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
✨ 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.
✨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.
December 28, 2024 at 1:55 AM
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.
✨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
🔎 CRISPR, HDR and deletions
🔎 Disease modelling and gene therapy
🔎 Screens
🔎 Delivery
December 28, 2024 at 1:55 AM
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
🔎 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!
December 28, 2024 at 1:55 AM
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!
3) BindCraft: one-shot design of functional protein binders. @martinpacesa.bsky.social
4) Rad51DBD-incorporated base editors improving zebrafish genome editing precision.
4) Rad51DBD-incorporated base editors improving zebrafish genome editing precision.
December 11, 2024 at 7:36 PM
3) BindCraft: one-shot design of functional protein binders. @martinpacesa.bsky.social
4) Rad51DBD-incorporated base editors improving zebrafish genome editing precision.
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.
Notable mentions:
1) Editing homologous globin genes with a nickase-deficient base editor to prevent large deletions.
2) Extended pegRNAs enhancing prime editing efficiency.
December 11, 2024 at 7:36 PM
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.
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.
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.
December 11, 2024 at 7:36 PM
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.
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.
3)Safe, precise ex vivo editing with PAM-less adenine base editors paired with high-fidelity variants and robust off-target analysis.
December 11, 2024 at 7:36 PM
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.
3)Safe, precise ex vivo editing with PAM-less adenine base editors paired with high-fidelity variants and robust off-target analysis.