CRISPR Gene Editing Newsletter
Issue #1September 8, 20257 studies

Scientists create 'one-shot' protein binders with 10-100% success rates + major CRISPR advances

Scientists create 'one-shot' protein binders with 10-100% success rates + major CRISPR advances

Monday, Monday, September 8th CRISPR Gene Editing Newsletter Issue #1

This week brought some serious breakthroughs in precision medicine - from AI designing custom protein binders in one try, to CRISPR editors that can modify 30 genes at once, to the first successful trial of off-the-shelf CAR-T cells treating lupus.

🎯 AI Designs Custom Protein Binders With 10-100% Success Rate

Researchers at the University of Washington created BindCraft, an AI system that designs custom protein binders with experimental success rates of 10-100% - no trial-and-error needed.

  • The system successfully created binders for challenging targets including CRISPR-Cas9, allergens, and cell-surface receptors, achieving nanomolar affinity (extremely tight binding)

  • In real-world tests, designed binders reduced allergic reactions to birch pollen in patient samples, controlled gene editing activity, and neutralized a bacterial toxin

  • They even used the binders to redirect virus delivery systems for targeted gene therapy

Why this matters: Until now, designing proteins that bind to specific targets required extensive lab screening and optimization. BindCraft's 'one design-one binder' approach could accelerate development of new therapeutics, diagnostics, and research tools.

🏆 Top 0.1% journal 🔗 Nature 🗓️ Aug 27

Key Findings

🧬 Off-the-Shelf CAR-T Cells Successfully Treat Lupus

All 5 patients with severe, treatment-resistant lupus achieved remission after receiving YTS109 - genetically modified T cells from healthy donors that target B cells. The cells were engineered using CRISPR to knock out 5 genes (including immune recognition genes) and insert a CD19-targeting system. Patients showed sustained improvement through 6 months with only mild side effects and no rejection.

💡 Manufacturing T cell therapies from healthy donors could make these treatments faster, cheaper, and more widely available than personalized versions.
🏆 Top 0.1% journal 🔗 Nature Medicine 🗓️ Aug 27

🔬 New CRISPR Tool Edits 30 Genes Simultaneously

Scientists engineered EOCas12i, a compact CRISPR system that achieved 3-60 fold better editing efficiency than the original version and can modify up to 30 genes at once using simple RNA arrays. The system performed comparably to widely-used CRISPR tools while producing longer deletions that may be better for knocking out genes completely.

💡 Multiplexed gene editing with compact tools could enable complex genetic modifications in a single treatment.
🥇 Top 1% journal 🔗 Nucleic Acids Research 🗓️ Aug 28

🎯 Safer CAR-T Manufacturing Using Multiple CRISPR Systems

Researchers combined two different CRISPR systems to create allogeneic CAR-T cells more safely - using base editors (no DNA breaks) to knock out 2 genes with 66-84% efficiency, while using traditional CRISPR to insert the CAR gene with up to 71% efficiency. This approach reduced dangerous chromosomal rearrangements by 210-fold compared to standard methods.

💡 Using gentler gene editing methods could make CAR-T cell manufacturing safer while maintaining effectiveness.
🥈 Top 2% journal 🔗 Molecular Therapy 🗓️ Aug 28

💡 Single Gene Therapy Treats Both Liver and Lung Disease

A compact base editor packaged in a single virus successfully treated alpha-1 antitrypsin deficiency in mice, achieving 23% gene correction after 8 weeks. The treatment restored protective protein levels above the therapeutic threshold and significantly improved lung function in animals with emphysema, while also reducing liver disease.

💡 One-virus gene therapies could treat genetic diseases affecting multiple organs simultaneously.
🥈 Top 2% journal 🔗 Molecular Therapy 🗓️ Aug 30

🧪 Epigenetic Editing Delivered as Temporary Treatment

Scientists developed RENDER, a system that temporarily delivers epigenome editors as protein complexes rather than permanent genetic modifications. The approach successfully silenced target genes across various human cell types including primary T cells and stem cell-derived neurons, and even reduced disease-associated mutant Tau protein in neurons.

💡 Temporary epigenetic modifications could provide therapeutic benefits without permanent genetic changes.
🥈 Top 2% journal 🔗 Nature Communications 🗓️ Aug 26

🔬 Cancer Vulnerability Discovered Through Gene Loss

CRISPR screening in small cell lung cancer revealed that tumors lacking NOTCH2 become dependent on TRIM28 for survival. When TRIM28 was removed from NOTCH2-deficient cancer cells, dormant viral sequences activated, triggering immune responses that killed the cancer cells. About 15% of small cell lung cancers have NOTCH mutations.

💡 Targeting TRIM28 could provide a new treatment strategy for NOTCH2-deficient lung cancers.
🥇 Top 1% journal 🔗 Developmental Cell 🗓️ Aug 27

Implications

These advances point toward a future of precision medicine where AI designs custom treatments, gene editing becomes safer and more versatile, and off-the-shelf cellular therapies replace expensive personalized manufacturing. The combination of better tools and smarter design could make advanced therapies more accessible and effective.

Studies in this issue

Primary sources used for this newsletter.

  1. Designing functional protein binders in a single step using BindCraft
    main storyNature2025-08-27PMID 40866699
  2. A small gene editor may improve liver and lung disease linked to AATD in mice
    key findingMolecular therapy : the journal of the American Society of Gene Therapy2025-08-30PMID 40883986
  3. Using separate CRISPR tools for precise gene insertion and multiple base changes to create off-the-shelf CAR-T cells without viruses
    key findingMolecular therapy : the journal of the American Society of Gene Therapy2025-08-28PMID 40873035
  4. Loss of NOTCH2 creates a TRIM28-related weakness in small cell lung cancer
    key findingDevelopmental cell2025-08-27PMID 40865518
  5. Controlling gene activity by temporarily delivering CRISPR-based epigenome editors
    key findingNature communications2025-08-26PMID 40858609
  6. Donor immune cells targeting CD19 for hard-to-treat lupus: a phase 1 trial
    key findingNature medicine2025-08-27PMID 40866583
  7. A CRISPR tool designed for efficient editing of multiple genes at once
    key findingNucleic acids research2025-08-28PMID 40867053

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