Lipid nanoparticles enabling gene therapies: from concepts to clinical utility

Jayesh A. Kulkarni, Pieter R. Cullis, Roy van der Meel

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

12 Citaties (Scopus)

Uittreksel

Genetic drugs based on RNA or DNA have remarkable therapeutic potential as virtually any disease can be treated by silencing a pathological gene, expressing a beneficial protein, or by editing defective genes. However, therapies based on nucleic acid polymers require sophisticated delivery systems to deliver these macromolecules to the interior of target cells. In this study, we review progress in developing nonviral lipid nanoparticle (LNP) delivery systems that have attractive properties, including ease of manufacture, reduced immune responses, multidosing capabilities, larger payloads, and flexibility of design. LNP systems represent the most advanced delivery systems for genetic drugs as it is expected that an LNP-short interfering RNA (siRNA) formulation will receive clinical approval from the Food and Drug Administration (FDA) in 2018 for treatment of the hereditary condition transthyretin-mediated amyloidosis, a fatal condition for which there is currently no treatment. This achievement is largely due to the development of optimized ionizable cationic lipids, arguably the most important factor in the clinical success of LNP-siRNA. In addition, we highlight potential LNP applications, including targeting tissues beyond the liver and therapeutic approaches based on messenger RNA or Clustered Regularly Interspaced Short Palindromic Repeats/Cas.

TaalEngels
Pagina's146-157
Aantal pagina's12
TijdschriftNucleic Acid Therapeutics
Volume28
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - jun 2018
Extern gepubliceerdJa

Vingerafdruk

Genetic Therapy
Nanoparticles
Lipids
Small Interfering RNA
Clustered Regularly Interspaced Short Palindromic Repeats
Therapeutics
United States Food and Drug Administration
Drug Delivery Systems
Nucleic Acids
Polymers
RNA
Messenger RNA
Liver
DNA
Pharmaceutical Preparations
Genes
Proteins

Citeer dit

Kulkarni, Jayesh A. ; Cullis, Pieter R. ; van der Meel, Roy. / Lipid nanoparticles enabling gene therapies : from concepts to clinical utility. In: Nucleic Acid Therapeutics. 2018 ; Vol. 28, Nr. 3. blz. 146-157
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Lipid nanoparticles enabling gene therapies : from concepts to clinical utility. / Kulkarni, Jayesh A.; Cullis, Pieter R.; van der Meel, Roy.

In: Nucleic Acid Therapeutics, Vol. 28, Nr. 3, 06.2018, blz. 146-157.

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

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