Evidence map›Paper›PMID 32347936›Full record

ArticleNucleic acids research2020

Generation and validation of structurally defined antibody-siRNA conjugates.

Alex R Nanna, Alexander V Kel'in, Christopher Theile, Justin M Pierson, Zhi Xiang Voo, Ashish Garg, Jayaprakash K Nair, Martin A Maier, Kevin Fitzgerald, Christoph Rader

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
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

30 citing papers in PubMed, 51 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

Alex R NannaDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Alexander V Kel'inAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Christopher TheileAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Justin M PiersonAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Zhi Xiang VooDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Ashish GargAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Jayaprakash K NairAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Martin A MaierAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Kevin FitzgeraldAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Christoph RaderDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Alnylam Pharmaceuticals (United States) · USScripps Research Institute · US

Funding

Novel Enediyne-Based Antibody-Drug Conjugates for CancersR01CA204484 · NCI · UNIVERSITY OF FLORIDA · PI Natarajan Muthusamy, Ben Shen · 2017 to 2026
$4.6M
NCI NIH HHS R01 CA204484
6 · The paper itself

Abstract

Gene silencing by RNA interference (RNAi) has emerged as a powerful treatment strategy across a potentially broad range of diseases. Tailoring siRNAs to silence genes vital for cancer cell growth and function could be an effective treatment, but there are several challenges which must be overcome to enable their use as a therapeutic modality, among which efficient and selective delivery to cancer cells remains paramount. Attempts to use antibodies for siRNA delivery have been reported but these strategies use either nonspecific conjugation resulting in mixtures, or site-specific methods that require multiple steps, introduction of mutations, or use of enzymes. Here, we report a method to generate antibody-siRNA (1:2) conjugates (ARCs) that are structurally defined and easy to assemble. This ARC platform is based on engineered dual variable domain (DVD) antibodies containing a natural uniquely reactive lysine residue for site-specific conjugation to β-lactam linker-functionalized siRNA. The conjugation is efficient, does not compromise the affinity of the parental antibody, and utilizes chemically stabilized siRNA. For proof-of-concept, we generated DVD-ARCs targeting various cell surface antigens on multiple myeloma cells for the selective delivery of siRNA targeting β-catenin (CTNNB1). A set of BCMA-targeting DVD-ARCs at concentrations as low as 10 nM revealed significant CTNNB1 mRNA and protein knockdown.

Indexed as

RNA InterferenceAntibodiesbeta CateninCell Line, TumorHumansImmunoglobulin Variable RegionRNA, Small InterferingAntibodiesbeta CateninCTNNB1 protein, humanImmunoglobulin Variable RegionRNA, Small Interfering

Identifiers

PMID32347936
PMCPMC7261152
OpenAlexW3019973694

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.