Genome Editing & Heritable Modification

[DD+TCR] A published alpha-1 antitrypsin deficiency case documents base correction directly in human liver tissue; Hannover reports seven treated patients and one off replacement infusions since March.

[SCAN+TCR] A light-activated gene-therapy trial reported restoration of aspects of visual function in the New England Journal of Medicine.

[DD+POD] Two teams solved tissue-targeting delivery for gene editors: a lipid screened for large cargo reached 48% editing in mouse brain and 27% in lung, while a chemically masked virus activated only by a light pulse or inflammation signal reached injured heart muscle carrying a blood-vessel-growth gene.

[DD+POD] CRMA-1001 used disabled Cas9 and methylation machinery to silence hepatitis B reservoirs without cutting host or viral DNA, showed no unintended human-genome edits in profiling, and entered trials in Hong Kong and New Zealand.

[DD+POD] Densely chemical-modified guide RNA armored along its entire length reached nearly 70% prime editing efficiency in mouse liver from a single lipid-nanoparticle injection at a clinically translatable dose, an approximately 80-fold gain over conventional end-protected guides.

[DD+POD] A Columbia University team led by Dieter Egli used base editing to correct every copy of PCSK9 in human embryos at fertilization, with edited embryos developing normally to the blastocyst stage despite persistent mosaic off-target edits and chromosomal deletions.

[DD+TCR] Donor-complementary prime editing (DoPE) achieved kilobase-scale DNA insertion using complementary sticky-end overhangs rather than a double-strand break, clearing a risk step long required by cut-and-repair insertion methods.

[DD+POD] EvoMax paired a protein language model with inverse-folding to design FanzMAX v3-hLa, a compact under-500-amino-acid gene editor that hit 97% efficiency at its best human target and knocked down hPCSK9 in mice via single-AAV delivery.

[DD+POD] Researchers used AlphaFold to identify protein regions responsible for off-target CRISPR edits and redesigned them to reduce error rates while preserving intended edits, improving safety of therapeutic editors already in clinical pipelines rather than building new ones.

[DD+POD] Science/Retraction Watch investigation found a six-year-old patient in a Shanghai base-editing trial died seven days post-infusion from a severe immune reaction, with the death and her family's ~$800,000 payment omitted from the team's Nature paper.

[DD+POD] KNIT inserted DNA payloads exceeding 10 kb at up to 89% efficiency without double-strand breaks, ContactSeek guided higher-fidelity editors, and a compact single-vector editor improved spinal muscular atrophy in mice.

[SCAN+TCR] Genetic-medicine veterans launched a center to standardize repeatable personalized CRISPR therapies, extending the one-off custom treatment that saved Baby KJ toward a reusable clinical pathway.

[DD+POD] AI-designed synthetic CRISPR nucleases derived from compact TnpB proteins outperformed natural editors at human gene editing while shrinking toward easier delivery, per Doudna-lab Science paper.

[DD+POD] A virus-like-particle carrier (tBE-VLP4) delivered base editing to liver (64.2%), a cholesterol gene (46%), and retina (24.2%) from a single injection with no detectable off-targets, alongside a new $160M ARPA-H custom-genetic-medicine program.

[DD+TCR] EU approved Novartis's Itvisma, an intrathecal SMA gene therapy, for patients from age 2 into adulthood, extending a therapy previously practical mainly for IV-treated infants to older, heavier patients, continuing the age-expansion pattern set by Casgevy's age-2 approval (07-02).

[SCAN+TCR] FDA expands Casgevy sickle-cell gene therapy approval to children as young as age 2, extending the youngest approved age for heritable-disease gene therapy.

[DD+POD] Retargeted Bxb1 large serine recombinase (Nature Biotechnology) achieved precise integration of large DNA payloads at researcher-chosen genomic locations without DNA cleavage, widening the set of sequences that can be precisely written into a genome and extending precision editing capability to cargo sizes impractical for CRISPR-based approaches.

[DD+TCR] Triple-knockout pig kidneys carrying added TNFAIP3 and HMOX1 human transgenes markedly prolonged primate xenograft survival and reduced immune-rejection infiltration (Nature Communications; eGenesis-supported): gene-edited donor-pig recipe narrowed from open-ended engineering to a defined target-transgene combination, converting organ-supply scarcity toward an engineering schedule.

[SCAN+TCR] Re-dosed AAV-hOTOF gene therapy restored hearing in four deaf children through pre-existing neutralizing antibodies in a second cochlear injection, lifting average thresholds from over 95 dB to 43 dB: first demonstration that re-dosing can thread past the antibody barrier that had confined cochlear gene therapy to one-treatment-per-ear protocols.

[DD] Lipid-nanoparticle-delivered prime editing achieved 49% in-vivo efficiency in mouse liver from a single low dose with a redosable synthetic carrier, fewer off-target edits than viral DNA delivery, and correction of PKU R408W to anticipated-curative phenylalanine levels, clearing the delivery bottleneck that confined in-vivo precision genome editing to viral one-shot approaches (Nature Nanotechnology).

[DD+POD] SMArT AND-gate selection raised CRISPR-HDR editing purity in human blood stem cells to 80-100%, widening the map of heritable blood disorders reachable by a single precise correction rather than a gene knockout.

Scribe Therapeutics' STX-1150 CRISPR-CasX epigenetic PCSK9 silencer sustained >50% LDL reduction for 22+ months from a single dose in non-human primates without altering DNA; Phase 1 enrollment begun in Australia: durable single-dose cardiovascular prevention without ongoing adherence or permanent genome modification.

Wake Forest, Duke, and Wisconsin labs jointly publish in PNAS that SP6/SP8 genes activate during regeneration in axolotls, zebrafish, and mice; CRISPR knockout of SP8 disabled axolotl bone rebuilding; viral gene therapy modeled on zebrafish regeneration enhancer carrying FGF8 partly restored mouse digit-bone regrowth.

Intellia's Phase 3 in-vivo CRISPR therapy lonvoguran ziclumeran cut hereditary angioedema attacks 87% vs. placebo, with 62% attack-free six months after one infusion.

FDA approved Regeneron's Otarmeni as the first gene therapy for genetic hearing loss, with the company committing to provide it free to eligible U.S. patients: first FDA approval of a hereditary-deafness gene therapy.

Nature reported ThermoCas9, a CRISPR variant that reads DNA methylation to selectively cut tumor DNA while sparing healthy cells; a Science Translational Medicine study showed methionine/arginine/serine supplementation boosted mRNA delivery up to 20x and single-dose CRISPR editing from ~25% to nearly 90%.

Karolinska Institutet (Nature Medicine): single cochlear OTOF gene therapy injection restored hearing in all 10 patients including teenagers and adults, average threshold improving from 106 dB to 52 dB within six months; researchers extending approach to GJB2 and TMC1 genes.

Penn researchers develop AI-guided gene therapy silencing chronic pain by targeting specific brain circuits, reproducing morphine's analgesia without activating addiction reward pathways: preclinical proof-of-concept.