Research Article

Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John’s University, Queens, NY 11439, USA

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Shraddha Bhutkar

Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John’s University, Queens, NY 11439, USA

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Ketan Patel

Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John’s University, Queens, NY 11439, USA

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Vikas V Dukhande

*Author for correspondence: Tel.: +1 7189902640;

E-mail Address: dukhandv@stjohns.edu

https://orcid.org/0000-0002-9288-715X

Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John’s University, Queens, NY 11439, USA

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Published Online:7 May 2021https://doi.org/10.2217/nnm-2020-0477

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Abstract

Aim: To develop novel cationic liposomes as a nonviral gene delivery vector for the treatment of rare diseases, such as Lafora disease – a neurodegenerative epilepsy. Materials & methods: DLinDMA and DOTAP liposomes were formulated and characterized for the delivery of gene encoding laforin and expression of functional protein in HEK293 and neuroblastoma cells. Results: Liposomes with cationic lipids DLinDMA and DOTAP showed good physicochemical characteristics. Nanosized DLinDMA liposomes demonstrated desired transfection efficiency, negligible hemolysis and minimal cytotoxicity. Western blotting confirmed successful expression and glucan phosphatase assay demonstrated the biological activity of laforin. Conclusion: Our study is a novel preclinical effort in formulating cationic lipoplexes containing plasmid DNA for the therapy of rare genetic diseases such as Lafora disease.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 16, No. 13

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History

Received 23 December 2020

Accepted 26 March 2021

Published online 7 May 2021

Published in print June 2021

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Keywords

Author contributions

Conceptualization was by VV Dukhande and K Patel. Methodology was performed by VV Dukhande, K Patel, HP Vemana, A Saraswat, SP Bhutkar. Validation was performed by VV Dukhande and K Patel. Formal analysis was performed by HP Vemana, A Saraswat. Investigation was performed by HP Vemana, A Saraswat, SP Bhutkar. Resources were provided VV Dukhande and K Patel. Data curation was performed by HP Vemana, A Saraswat, SP Bhutkar. Original draft preparation was performed by HP Vemana, A Saraswat. Review and editing were performed by VV Dukhande and K Patel. Visualization was performed by VV Dukhande and K Patel. Supervision was performed by VV Dukhande and K Patel. Project administration was performed by VV Dukhande and K Patel.

Financial & competing interests disclosure

This research was supported by an award from the National Institute of General Medical Sciences of the NIH under Award Number SC2GM125550 to VV Dukhande and by funds from the College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, USA to VV Dukhande and K Patel. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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A novel gene therapy for neurodegenerative Lafora disease via EPM2A-loaded DLinDMA lipoplexes

Abstract

Graphical abstract

References