Evidence map›Paper›PMID 38014030›Full record

ArticlebioRxiv : the preprint server for biology2023

Directed Evolution of Genetically Encoded LYTACs for Cell-Mediated Delivery.

Jonathan Lee Yang, Sean A Yamada-Hunter, Louai Labanieh, Elena Sotillo, Joleen S Cheah, David S Roberts, Crystal L Mackall, Alice Y Ting, Carolyn R Bertozzi

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, 4 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Jonathan Lee YangDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3378-1379
Sean A Yamada-HunterCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Louai LabaniehDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Elena SotilloDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Joleen S CheahDepartments of Biology, and Genetics Stanford University, Stanford, CA 94305, USA.
David S RobertsDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Crystal L MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alice Y TingDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Carolyn R BertozziDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Stanford University · USChan Zuckerberg Initiative (United States) · USHoward Hughes Medical Institute · USParker Institute for Cancer Immunotherapy · USPediatrics and Genetics · US

Funding

METABOLIC OLIGOSACCHARIDE ENGINEERINGR01GM058867 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Carolyn Bertozzi · 1999 to 2026
$5.6M
NexTGen - STANFORDOT2CA278686 · NCI · STANFORD UNIVERSITY · PI Carolyn Bertozzi · 2022 to 2026
$1.2M
NCI NIH HHS OT2 CA278686NIGMS NIH HHS R01 GM058867
6 · The paper itself

Abstract

Lysosome-targeting chimeras (LYTACs) are a promising therapeutic modality to drive the degradation of extracellular proteins. However, early versions of LYTAC contain synthetic glycopeptides that cannot be genetically encoded. Here we present our designs for a fully genetically encodable LYTAC (GELYTAC), making our tool compatible with integration into therapeutic cells for targeted delivery at diseased sites. To achieve this, we replaced the glycopeptide portion of LYTACs with the protein insulin like growth factor 2 (IGF2). After showing initial efficacy with wild type IGF2, we increased the potency of GELYTAC using directed evolution. Subsequently, we demonstrated that our engineered GELYTAC construct not only secretes from HEK293T cells but also from human primary T-cells to drive the uptake of various targets into receiver cells. Immune cells engineered to secrete GELYTAC thus represent a promising avenue for spatially-selective targeted protein degradation.

Indexed as

Cell therapyChemical biologysynthetic biologyTargeted protein degradation

Identifiers

PMID38014030
PMCPMC10680704
OpenAlexW4388725329

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.