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Review
. 2024 Jun 18;22(1):343.
doi: 10.1186/s12951-024-02627-w.

Nanomaterials-assisted gene editing and synthetic biology for optimizing the treatment of pulmonary diseases

Lanjie Lei #  1 , Wenjie Pan #  2 , Xin Shou  1 , Yunyuan Shao  1 , Shuxuan Ye  1 , Junfeng Zhang  3 , Narasaiah Kolliputi  4 , Liyun Shi  5
Affiliations
Review

Nanomaterials-assisted gene editing and synthetic biology for optimizing the treatment of pulmonary diseases

Lanjie Lei et al. J Nanobiotechnology. .

Abstract

The use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives.

Keywords: Gene editing; Nanomaterials; Pulmonary diseases; Synthetic biology.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of potential nanocarriers and their AD-dependent deposition and distribution mechanisms in the respiratory system. Adapted from Refs [42, 50]
Fig. 2
Fig. 2
(A) Schematic representation of ROS responsive liposome-DTP@DMF NPs synthesis and therapeutic mechanism [83]. (B) pH-responsive polymer delivery system methoxy-PEG (mPEG)-pH-sensitive polymer bearing a seven-membered ring with a tertiary amine (PC7A) NPs for Cas9 ribonucleoprotein (RNP) and single-strand oligonucleotides (ssODN) delivery [86]. (a) Schematic representation of mPEG-PC7A NPs synthesis and entry into cells. (b-d) Gene editing in vivo using delivering Cas9 RNP alone (non-homologous end joining-NP) in Ai14 mouse lungs by intratracheal injection. Reprinted with permission from Ref [83, 86]
Fig. 3
Fig. 3
(A) Coronavirus S protein-modified dendritic MSNs to deliver specific siRNAs to treat SARS-CoV-2 infection [114]. (B) Cu/Zn bimetallic MOF nanoplatforms capable of encapsulating therapeutic deoxyribozymes (DNAzymes) for intracellular drug synthesis and gene therapy [116]. Reprinted with permission from Ref [114, 116]
Fig. 4
Fig. 4
(A) Acyclic acetal-based nanoparticles for viral therapy of NSCLC [198]. (a) Synthetic route of acyclic acetal-based nanoparticles. (b) Targeted delivery of acyclic acetal-based nanoparticles. (c) Effect of pH conditions of tumor microenvironment on acyclic acetal-based nanoparticles. (d) In vivo luminescence images of luciferase after injection of acyclic acetal-based nanoparticles or adeno-associated virus serotype 2. (B) Lipid-coated MSNs for CRISPR delivery [199]. (a) Synthetic route of CRISPR@LC-MSN. (b) Transmission electron microscopy characterization of MSNs and RNP@LC-MSNs. (c-d) Cellular uptake of LC-MSN. (C) A carrier-free ternary Cas9 RNP delivery system for in vitro and in vivo gene editing [200]. (a) Ternary Cas9 RNP delivery system for KRAS treatment in NSCLC. (b) KRAS expression in different cells after delivery of three Cas9 RNPs. (c) Ternary Cas9 RNPs inhibited KRAS expression. (D) PS@HA-Lip for targeted delivery of mutT homolog1 plasmid (pMTH1) for NSCLC therapy [201]. (a) Synthetic route of DSPE-PEG-HA. (b) Mechanism of PS@HA-Lip/pMTH1 for NSCLC therapy. Reprinted with permission from Ref [–201]
Fig. 5
Fig. 5
(A) SORT-LNP prepared by adding different SORT molecules to traditional LNP for targeting different organs [208]. (B) LNPs optimization for delivery of nebulized therapeutic mRNA to the lungs [209]. (a) Optimizing LNP-targeted lung delivery. (b) Mole ratio of NLD1 components. (c) Expression of NLD1 carrying AncNanoLuc mRNA in different tissues of mice. (d) Survival of H1V1-injected mice treated with NLD1 was 100%. Reprinted with permission from Ref [208, 209]
Fig. 6
Fig. 6
(A) Functionalized nano-delivery vector protamine sulfate stabilized Au NPs (AuPS)@pDNA for the treatment of IPF [231]. (a) Synthesis and therapeutic mechanism of AuPS@pDNA. (b) AuPS@pDNA-tagged hMSCs inhibit lung fibrosis in IPF cell model. (c) Three-dimensional computer tomography (CT) imaging of AuPS@pDNA-labeled hMSCs transplanted into the lungs of IPF mice. (B) Inhaled siIL11@PPGC NPs for the treatment of lung fibrosis [232]. (a) Inhaled siIL11@PPGC NPs into mouse lung fibroblasts for IPF treatment. (b) Inhalation therapy experimental design. (c-d) Lung tissue images (c) and immunofluorescence staining (d) of lung tissues of mice in different treatment groups. Reprinted with permission from Ref [231, 232]
Fig. 7
Fig. 7
(A) A CRISPR/Cas12-based assay for detection of SARS-CoV-2 [250]. (a) Primers, probes, and gRNA for genome. (b) SARS-CoV-2 DETECTR workflow. (B) SHARK-based RNA sensing for SARS-CoV-2 detection [249]. (a) SHARK workflow. (b) SARS-CoV-2 detection. (c) Optimization of crRNA types in SHARK. (d) SHARK assay for different concentrations of viral RNAs. (e) Results based on the SHARK device assay were consistent with the Ct values of qRT-PCR. Reprinted with permission from Ref [249, 250]
Fig. 8
Fig. 8
(A) SARS-CoV-2 miniprotein inhibitors [254]. (a) Cryo–electron microscopy structures of SARS-CoV-2 S bound to LCB1. (b-c) Design of miniprotein inhibitors to neutralize live viruses. (B) A trivalent nano-some that neutralizes SARS-CoV-2 by stabilizing inactivated Spike [255]. (a) Cryo–electron microscopy structures of SpikeS2P-Nb6 complex. (b) mNb6-tri inhibits SARS-CoV-2 infection after lyophilization or heat treatment. Reprinted with permission frH
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References

    1. Christenson SA, Smith BM, Bafadhel M, Putcha N. Chronic obstructive pulmonary disease. Lancet. 2022;399(10342):2227–42. doi: 10.1016/S0140-6736(22)00470-6. - DOI - PubMed
    1. Stolz D, Mkorombindo T, Schumann DM, Agusti A, Ash SY, Bafadhel M, Bai C, Chalmers JD, Gerard JC, Dharmage SC, et al. Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. Lancet. 2022;400(10356):921–72. doi: 10.1016/S0140-6736(22)01273-9. - DOI - PubMed
    1. Celli BR, Wedzicha JA. Update on clinical aspects of chronic obstructive pulmonary disease. N Engl J Med. 2019;381(13):1257–66. doi: 10.1056/NEJMra1900500. - DOI - PubMed
    1. Burgel P-R, Burnet E, Regard L, Martin C. The changing epidemiology of cystic fibrosis the implications for adult care. Chest. 2023;163(1):89–99. doi: 10.1016/j.chest.2022.07.004. - DOI - PubMed
    1. Kanne JP, Little BP, Schulte JJ, Haramati A, Haramati LB. Long-term lung abnormalities associated with covid-19 pneumonia. Radiology 2023, 306(2). - PMC - PubMed