Evidence map›Paper›PMID 41993426›Full record

ArticlebioRxiv : the preprint server for biology2026

Ultra-large targeted DNA integrations in primary human cells.

Courtney Kernick, Lauren Chow, Mikail Alejandro, Ke Li, Maxwell G Foisey, Xiaoyu Yang, Claire Hilburger, Johnathan Lu, Lujing Wu, Alison McClellan and 28 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors.

Courtney KernickDepartment of Pathology, Stanford University, Stanford, CA, USA.
Lauren ChowDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Mikail AlejandroDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Ke LiDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Maxwell G FoiseyDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Xiaoyu YangDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Claire HilburgerDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Johnathan LuDepartment of Pathology, Stanford University, Stanford, CA, USA.
Lujing WuDepartment of Pathology, Stanford University, Stanford, CA, USA.
Alison McClellanDepartment of Pathology, Stanford University, Stanford, CA, USA.
Oliver Takacsi-NagyDepartment of Pathology, Stanford University, Stanford, CA, USA.
Rocco BrajenovicDepartment of Pathology, Stanford University, Stanford, CA, USA.
Nicole E TheberathDepartment of Pathology, Stanford University, Stanford, CA, USA.
Emily Celallos FuentesDepartment of Pathology, Stanford University, Stanford, CA, USA.
Erin LinDepartment of Pathology, Stanford University, Stanford, CA, USA.
Austin HartmanDepartment of Pathology, Stanford University, Stanford, CA, USA.
Tina TruongDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Jae Hyun Jenny LeeDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Luke WorkleyDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Alvin S HaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Yongchang JiThermo Fisher Scientific, Carlsbad, CA USA.
Nicholas PutnamThermo Fisher Scientific, Carlsbad, CA USA.
Nektaria AndronikouThermo Fisher Scientific, Carlsbad, CA USA.
Nujhat FatimaThermo Fisher Scientific, Carlsbad, CA USA.
Max DotsonThermo Fisher Scientific, Carlsbad, CA USA.
Kimberly A WongKano Therapeutics Inc., Cambridge, MA, USA.
Christian H BurnsKano Therapeutics Inc., Cambridge, MA, USA.
Floris A S EngelhardKano Therapeutics Inc., Cambridge, MA, USA.
Elena StoyanovaTouchlight, Hampton, England, UK.
Milica VukovicTouchlight, Hampton, England, UK.
Tom AdieTouchlight, Hampton, England, UK.
Wendell A LimDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Kole RoybalGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Katherine SantostefanoDepartment of Pathology, Stanford University, Stanford, CA, USA.
Ricardo AlmeidaDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Greg M AllenDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Brian R ShyDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Theodore L RothDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-3970-9573

Funding

Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Developing novel CAR T cell designs using combinatorial antigen detectionK08CA259610 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALLEN, GREG MANESS · 2021 to 2025
$1.4M
Synthetic Cell State Engineering for Primary Human Cellular TherapiesDP2CA311217 · NCI · STANFORD UNIVERSITY · PI ROTH, THEODORE LEE · 2025 to 2025
$1.4M
Non-viral genome, epigenome, and transcriptome engineering for clinical CAR-T cell manufacturingK08CA273529 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian R Shy · 2022 to 2026
$1.2M
Dissecting intrinsic variability in engineered T Cell immunotherapiesK08CA286740 · NCI · STANFORD UNIVERSITY · PI Theodore Lee Roth · 2024 to 2026
$747k
NCATS NIH HHS L30 TR002983NCI NIH HHS DP2 CA311217NCI NIH HHS K08 CA259610NCI NIH HHS K08 CA273529NCI NIH HHS K08 CA286740NIGMS NIH HHS T32 GM136547
6 · The paper itself

Abstract

Genetic engineering experiments and therapies are constrained by the size of DNA integrations into human cell's genomes. Existing AAV, lentiviral, and non-viral methods rapidly decrease in integration efficiency beyond ~5kb of sequence. Through systematic evaluation of non-viral DNA template formats, we identified circular ssDNA and dsDNA as capable of mediating >5kb integrations. Large circular DNA delivery efficiency and its impacts on cell viability and payload expression could be significantly improved with small DNA "helper" plasmids, mRNA-encoded nucleases, and sequence design optimizations. Collectively, these modifications enabled ultra-large-up to 10 kb DNA-integrations at >20% efficiency in primary human T cells at the

Identifiers

PMID41993426
PMCPMC13081881

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.