Delivery Platforms for CRISPR/Cas9 Genome Editing of Glial Cells in the Central Nervous System

Overview

Journal Front Genome Ed

Date 2021 Oct 29

PMID 34713256

Citations 8

Authors

Vasco Meneghini

Marco Peviani

Marco Luciani

Giada Zambonini

Angela Gritti

Affiliations

Soon will be listed here.

Abstract

Glial cells (astrocytes, oligodendrocytes, and microglia) are emerging as key players in several physiological and pathological processes of the central nervous system (CNS). Astrocytes and oligodendrocytes are not only supportive cells that release trophic factors or regulate energy metabolism, but they also actively modulate critical neuronal processes and functions in the tripartite synapse. Microglia are defined as CNS-resident cells that provide immune surveillance; however, they also actively contribute to shaping the neuronal microenvironment by scavenging cell debris or regulating synaptogenesis and pruning. Given the many interconnected processes coordinated by glial cells, it is not surprising that both acute and chronic CNS insults not only cause neuronal damage but also trigger complex multifaceted responses, including neuroinflammation, which can critically contribute to the disease progression and worsening of symptoms in several neurodegenerative diseases. Overall, this makes glial cells excellent candidates for targeted therapies to treat CNS disorders. In recent years, the application of gene editing technologies has redefined therapeutic strategies to treat genetic and age-related neurological diseases. In this review, we discuss the advantages and limitations of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based gene editing in the treatment of neurodegenerative disorders, focusing on the development of viral- and nanoparticle-based delivery methods for glial cell targeting.

Citing Articles

Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation: neuronal regeneration strategies for Parkinson's and Alzheimer's disease.

McDowall S, Bagda V, Hodgetts S, Mastaglia F, Li D Transl Neurodegener. 2024; 13(1):59.

PMID: 39627843 PMC: 11613593. DOI: 10.1186/s40035-024-00450-9.

Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.

Zhang H, Kelly K, Lee J, Echeverria D, Cooper D, Panwala R Nucleic Acids Res. 2023; 52(2):977-997.

PMID: 38033325 PMC: 10810193. DOI: 10.1093/nar/gkad1125.

Oligodendrocyte progenitor cells in Alzheimer's disease: from physiology to pathology.

Zou P, Wu C, Liu T, Duan R, Yang L Transl Neurodegener. 2023; 12(1):52.

PMID: 37964328 PMC: 10644503. DOI: 10.1186/s40035-023-00385-7.

An Update on the Application of CRISPR Technology in Clinical Practice.

Morshedzadeh F, Ghanei M, Lotfi M, Ghasemi M, Ahmadi M, Najari-Hanjani P Mol Biotechnol. 2023; 66(2):179-197.

PMID: 37269466 PMC: 10239226. DOI: 10.1007/s12033-023-00724-z.

Recent advances in the use of CRISPR/Cas for understanding the early development of molecular gaps in glial cells.

Barragan-Alvarez C, Flores-Fernandez J, Hernandez-Perez O, Avila-Gonzalez D, Diaz N, Padilla-Camberos E Front Cell Dev Biol. 2022; 10:947769.

PMID: 36120556 PMC: 9479146. DOI: 10.3389/fcell.2022.947769.

References

Polstein L, Perez-Pinera P, Kocak D, Vockley C, Bledsoe P, Song L . Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators. Genome Res. 2015; 25(8):1158-69. PMC: 4510000. DOI: 10.1101/gr.179044.114. View

Hirai H, Tani T, Kikyo N . Structure and functions of powerful transactivators: VP16, MyoD and FoxA. Int J Dev Biol. 2011; 54(11-12):1589-96. PMC: 3419751. DOI: 10.1387/ijdb.103194hh. View

Janowska J, Gargas J, Ziemka-Nalecz M, Zalewska T, Buzanska L, Sypecka J . Directed glial differentiation and transdifferentiation for neural tissue regeneration. Exp Neurol. 2018; 319:112813. DOI: 10.1016/j.expneurol.2018.08.010. View

Deverman B, Ravina B, Bankiewicz K, Paul S, Sah D . Gene therapy for neurological disorders: progress and prospects. Nat Rev Drug Discov. 2018; 17(9):641-659. DOI: 10.1038/nrd.2018.110. View

Kondo T, Funayama M, Miyake M, Tsukita K, Era T, Osaka H . Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes. Acta Neuropathol Commun. 2016; 4(1):69. PMC: 4940830. DOI: 10.1186/s40478-016-0337-0. View

Maeder M, Linder S, Cascio V, Fu Y, Ho Q, Joung J . CRISPR RNA-guided activation of endogenous human genes. Nat Methods. 2013; 10(10):977-9. PMC: 3794058. DOI: 10.1038/nmeth.2598. View

Michinaga S, Koyama Y . Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage. Int J Mol Sci. 2019; 20(3). PMC: 6387062. DOI: 10.3390/ijms20030571. View

Yeh W, Chiang H, Rees H, Edge A, Liu D . In vivo base editing of post-mitotic sensory cells. Nat Commun. 2018; 9(1):2184. PMC: 5988727. DOI: 10.1038/s41467-018-04580-3. View

Lafourcade C, Ramirez J, Luarte A, Fernandez A, Wyneken U . MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity. J Exp Neurosci. 2016; 10(Suppl 1):1-9. PMC: 4978198. DOI: 10.4137/JEN.S39916. View

10.

Perez-Pinera P, Kocak D, Vockley C, Adler A, Kabadi A, Polstein L . RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods. 2013; 10(10):973-6. PMC: 3911785. DOI: 10.1038/nmeth.2600. View

11.

Chen G, Abdeen A, Wang Y, Shahi P, Robertson S, Xie R . A biodegradable nanocapsule delivers a Cas9 ribonucleoprotein complex for in vivo genome editing. Nat Nanotechnol. 2019; 14(10):974-980. PMC: 6778035. DOI: 10.1038/s41565-019-0539-2. View

12.

Tufail Y, Cook D, Fourgeaud L, Powers C, Merten K, Clark C . Phosphatidylserine Exposure Controls Viral Innate Immune Responses by Microglia. Neuron. 2017; 93(3):574-586.e8. PMC: 5600182. DOI: 10.1016/j.neuron.2016.12.021. View

13.

Foust K, Nurre E, Montgomery C, Hernandez A, Chan C, Kaspar B . Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2008; 27(1):59-65. PMC: 2895694. DOI: 10.1038/nbt.1515. View

14.

Liu Q, Wang C, Zheng Y, Zhao Y, Wang Y, Hao J . Virus-like nanoparticle as a co-delivery system to enhance efficacy of CRISPR/Cas9-based cancer immunotherapy. Biomaterials. 2020; 258:120275. DOI: 10.1016/j.biomaterials.2020.120275. View

15.

Earley L, Conatser L, Lue V, Dobbins A, Li C, Hirsch M . Adeno-Associated Virus Serotype-Specific Inverted Terminal Repeat Sequence Role in Vector Transgene Expression. Hum Gene Ther. 2020; 31(3-4):151-162. PMC: 7047122. DOI: 10.1089/hum.2019.274. View

16.

Zhang X, Zhao W, Nguyen G, Zhang C, Zeng C, Yan J . Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing. Sci Adv. 2020; 6(34). PMC: 7442477. DOI: 10.1126/sciadv.abc2315. View

17.

Kleinstiver B, Pattanayak V, Prew M, Tsai S, Nguyen N, Zheng Z . High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016; 529(7587):490-5. PMC: 4851738. DOI: 10.1038/nature16526. View

18.

Chavez A, Scheiman J, Vora S, Pruitt B, Tuttle M, Iyer E . Highly efficient Cas9-mediated transcriptional programming. Nat Methods. 2015; 12(4):326-8. PMC: 4393883. DOI: 10.1038/nmeth.3312. View

19.

Butterworth R . Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy. Neurochem Int. 2010; 57(4):383-8. DOI: 10.1016/j.neuint.2010.03.012. View

20.

Hanlon K, Meltzer J, Buzhdygan T, Cheng M, Sena-Esteves M, Bennett R . Selection of an Efficient AAV Vector for Robust CNS Transgene Expression. Mol Ther Methods Clin Dev. 2019; 15:320-332. PMC: 6881693. DOI: 10.1016/j.omtm.2019.10.007. View