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Record W3164967630 · doi:10.1038/s41565-021-00898-0

The current landscape of nucleic acid therapeutics

2021· review· en· W3164967630 on OpenAlexafffund
Jayesh A. Kulkarni, Dominik Witzigmann, Sarah B. Thomson, Sam Chen, Blair R. Leavitt, Pieter R. Cullis, Roy van der Meel

Bibliographic record

VenueNature Nanotechnology · 2021
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsBC Children's HospitaliCo Therapeutics (Canada)University of British Columbia
FundersSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungHuntington Society of CanadaGovernment of CanadaFondation Brain CanadaNederlandse Organisatie voor Wetenschappelijk OnderzoekWeston Brain InstituteCanadian Institutes of Health ResearchNanoMedicines Innovation Network
KeywordsNucleic acidComputational biologyOligonucleotideTranslation (biology)RNA interferenceSmall interfering RNANanotechnologyBiologyRNAComputer scienceBioinformaticsDNAGeneGeneticsMessenger RNAMaterials science

Abstract

fetched live from OpenAlex

The increasing number of approved nucleic acid therapeutics demonstrates the potential to treat diseases by targeting their genetic blueprints in vivo. Conventional treatments generally induce therapeutic effects that are transient because they target proteins rather than underlying causes. In contrast, nucleic acid therapeutics can achieve long-lasting or even curative effects via gene inhibition, addition, replacement or editing. Their clinical translation, however, depends on delivery technologies that improve stability, facilitate internalization and increase target affinity. Here, we review four platform technologies that have enabled the clinical translation of nucleic acid therapeutics: antisense oligonucleotides, ligand-modified small interfering RNA conjugates, lipid nanoparticles and adeno-associated virus vectors. For each platform, we discuss the current state-of-the-art clinical approaches, explain the rationale behind its development, highlight technological aspects that facilitated clinical translation and provide an example of a clinically relevant genetic drug. In addition, we discuss how these technologies enable the development of cutting-edge genetic drugs, such as tissue-specific nucleic acid bioconjugates, messenger RNA and gene-editing therapeutics. This Review provides an overview of four platform technologies that are currently used in the clinic for delivery of nucleic acid therapeutics, describing their properties, discussing technical advancements that led to clinical approval, and highlighting examples of approved genetic drugs that make use of these technologies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.007
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0070.004

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.323
Teacher spread0.305 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1,288
Published2021
Admission routes2
Has abstractyes

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