Peptide nanoparticle delivery of charge-neutral splice-switching morpholino oligonucleotides.

Järver, PeterMedical Research Council , Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom (författare)

Oligonucleotide analogs have provided novel therapeutics targeting various disorders. However, their poor cellular uptake remains a major obstacle for their clinical development. Negatively charged oligonucleotides, such as 2'-O-Methyl RNA and locked nucleic acids have in recent years been delivered successfully into cells through complex formation with cationic polymers, peptides, liposomes, or similar nanoparticle delivery systems. However, due to the lack of electrostatic interactions, this promising delivery method has been unsuccessful to date using charge-neutral oligonucleotide analogs. We show here that lipid-functionalized cell-penetrating peptides can be efficiently exploited for cellular transfection of the charge-neutral oligonucleotide analog phosphorodiamidate morpholino. The lipopeptides form complexes with splice-switching phosphorodiamidate morpholino oligonucleotide and can be delivered into clinically relevant cell lines that are otherwise difficult to transfect while retaining biological activity. To our knowledge, this is the first study to show delivery through complex formation of biologically active charge-neutral oligonucleotides by cationic peptides.

Zaghloul, Eman MKarolinska Institutet (författare)
Arzumanov, Andrey AMedical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom (författare)
Saleh, Amer FMedical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom (författare)
McClorey, GrahamDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom (författare)
Hammond, Suzan MDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom (författare)
Hällbrink, MattiasDepartment of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden(Swepub:su)mhall (författare)
Langel, ÜloStockholms universitet,Institutionen för neurokemi(Swepub:su)ulo (författare)
Smith, C I EdvardKarolinska Institutet (författare)
Wood, Matthew J ADepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom (författare)
Gait, Michael JMedical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom (författare)
El Andaloussi, SamirKarolinska Institutet (författare)
Karolinska InstitutetMedical Research Council , Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom (creator_code:org_t)

Ingår i:Nucleic Acid Therapeutics: Mary Ann Liebert Inc25:2, s. 65-772159-33372159-3345

Av författaren/redakt...: Järver, Peter; Zaghloul, Eman M; Arzumanov, Andre ...; Saleh, Amer F; McClorey, Graham; Hammond, Suzan M; visa fler...; Hällbrink, Matti ...; Langel, Ülo; Smith, C I Edvar ...; Wood, Matthew J ...; Gait, Michael J; El Andaloussi, S ...; visa färre...

Om ämnet

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.