Evidence map›Paper›PMID 36993169›Full record

ArticlebioRxiv : the preprint server for biology2023

Self-delivering CRISPR RNAs for AAV Co-delivery and Genome Editing

Han Zhang, Karen Kelly, Jonathan Lee, Dimas Echeverria, David Cooper, Rebecca Panwala, Zexiang Chen, Nicholas Gaston, Gregory A Newby, Jun Xie and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Han ZhangRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Karen KellyRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Jonathan LeeRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Dimas EcheverriaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
David CooperRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Rebecca PanwalaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Zexiang ChenRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Nicholas GastonRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, 02142, USA.
Jun XieHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, 02142, USA.
Guangping GaoHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Scot A WolfeLi Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Jonathan K WattsRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, 01605, USA.
University of Massachusetts Chan Medical School · USBroad Institute · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUH3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2021 to 2022
$3.1M
Delivery Technologies for In Vivo Genome EditingUG3AI150551 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2019 to 2021
$2.3M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
In vivo precision genome editing to correct genetic diseaseR00HL163805 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI NEWBY, GREGORY A. · 2023 to 2025
$747k
BD FACSAriaTM Fusion Fluoresence-Activated Cell SorterS10OD028576 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHRADER, CAROL E · 2020 to 2020
$565k
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
In vivo precision genome editing to correct genetic diseaseK99HL163805 · NHLBI · BROAD INSTITUTE, INC. · PI NEWBY, GREGORY A. · 2022 to 2022
$167k
NCATS NIH HHS UH3 TR002668NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS K99 HL163805NHLBI NIH HHS R00 HL163805NIAID NIH HHS U01 AI142756NIAID NIH HHS UG3 AI150551NIGMS NIH HHS R35 GM118062NIH HHS S10 OD020012NIH HHS S10 OD028576
6 · The paper itself

Abstract

Guide RNAs offer programmability for CRISPR-Cas9 genome editing but also add challenges for delivery. Chemical modification, which has been key to the success of oligonucleotide therapeutics, can enhance the stability, distribution, cellular uptake, and safety of nucleic acids. Previously, we engineered heavily and fully modified SpyCas9 crRNA and tracrRNA, which showed enhanced stability and retained activity when delivered to cultured cells in the form of the ribonucleoprotein complex. In this study, we report that a short, fully stabilized oligonucleotide (a "protecting oligo"), which can be displaced by tracrRNA annealing, can significantly enhance the potency and stability of a heavily modified crRNA. Furthermore, protecting oligos allow various bioconjugates to be appended, thereby improving cellular uptake and biodistribution of crRNA

Identifiers

PMID36993169
PMCPMC10055305
OpenAlexW4328112935

What OpenQuestion holds

Textmetadata
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.