Abstract
Neuronal direct cell reprogramming approach allows direct conversion of somatic cells into neurons via forced expression of neuronal cell-lineage transcription factors (TFs). These so-called induced neuronal cells have significant potential as research tools and for therapeutic applications, such as in cell replacement therapy. However, the optimization of TF delivery strategies is crucial to reach clinical practice. In this review, we outlined the currently explored delivery technologies in neuronal direct cell reprogramming and their limitations and advantages. The first employed delivery strategies were mainly integrating viral systems, such as lentiviruses that exert consistently high transgene expression in most cell types. On the other hand, viral systems cause major safety concerns, including the risk for insertional mutagenesis and inflammation. More recently, several safer nonviral delivery systems have been investigated as well; however, these systems generally exert inferior reprogramming efficiency compared with viral systems. Emerging delivery technologies could provide new opportunities in the achievement of safe and effective delivery for neuronal direct cell reprogramming.
| Original language | English |
|---|---|
| Pages (from-to) | 109-123 |
| Number of pages | 15 |
| Journal | Cellular Reprogramming |
| Volume | 27 |
| Issue number | 3 |
| Early online date | 30 May 2025 |
| DOIs | |
| Publication status | Published - Jun 2025 |
Bibliographical note
Publisher Copyright:Copyright 2025, Mary Ann Liebert, Inc., publishers.
Funding
We acknowledge financial support by European\u2019s Union\u2019s Horizon 2020 research and innovation programme under grant agreement n. 964497 (ENLIGHT) and under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.1, Call for tender No. 1409 published on September 14, 2022, by the Italian Ministry of University and Research (MUR), funded by the European Union\u2019s NextGenerationEU Project Title: \u201CModulation of dopaminergic transmission through microRNAs as a measure to counteract dopamine neuronal degeneration\u201D\u2014CUP: E53D23018200001, Grant Assignment Decree No. 1065 adopted on July 18, 2023, by the Italian Ministry of Ministry of University and Research (MUR).
| Funders | Funder number |
|---|---|
| Ministero dell'Università e della Ricerca | |
| National Recovery and Resilience Plan | |
| Ministero dell’Istruzione, dell’Università e della Ricerca | |
| European’s Union’s Horizon 2020 research and innovation programme | 964497 |
| European Commission | E53D23018200001, 1065 |
Keywords
- adeno-associated virus
- cell reprogramming
- delivery systems
- lentivirus
- neurodegenerative diseases
- nonviral delivery