Harnessing lipid nanoparticles for efficient CRISPR delivery

2021 ◽  
Author(s):  
Jingyue Yan ◽  
Diana D. Kang ◽  
Yizhou Dong
Keyword(s):  
Infectious Diseases ◽  
Genetic Disorders ◽  
Lipid Nanoparticles

Lipid-based nanomaterials have shown to mediate specific and effective CRISPR delivery in vivo for the treatment of various diseases, including cancers, genetic disorders and infectious diseases.

scholarly journals A review: Possible optimization of Cas9-sgRNA nuclease delivery via ingested lipid nanoparticles bioencapsulated within plant cell-based enfolding

2019 ◽  
Author(s):  
Tatiana Hillman
Keyword(s):  
Dna Sequences ◽  
Genetic Disorders ◽  
Single Point ◽  
Lipid Nanoparticles ◽  
Single Point Mutation ◽  
Cas9 Nuclease ◽  
Target Dna ◽  
Effective Delivery ◽  
Sgrna Design

The possibility of gene editing to correct disorders is one of the most impactful therapeutic agents, currently. CRISPR Cas9-sgRNA nucleases can be used to cleave and to delete harmful or pathogenic DNA sequences, which cause genetic disorders. Cas9 nuclease includes palindromic repeats that cut and delete a single point mutation or multiple DNA target site sequences. The Cas9, attached to a sgRNA or a guiding RNA, finds and then cleaves the target DNA sequence. The Cas9-sgRNA method of cleavage has corrected DNA mutations that cause cataracts in the eyes, cystic fibrosis, and chronic granulomatous disease. However, there are issues with an effective delivery of Cas9-sgRA to target DNA sequences. Delivering Cas-9 nucleases are negatively affected by off-target DNA sites, sgRNA design, off-target cleavage, Cas9 activation, and the method of delivery. This review focuses on oral and ingested delivery methods to effectively guide the transport of Cas9-sgRNA nucleases in vivo. This review presents possible alternatives for nuclease delivery within optimized lipid-nanoparticles, plant, algae, and bacterial-based orally ingested edibles. This review attempts to provide evidence in support of the higher effectiveness of ingesting therapeutic bioencapsulated edibles because the edibles can directly contact immune cells within the gastrointestinal tract for blood or lymph circulation.

scholarly journals A review: Possible optimization of Cas9-sgRNA nuclease delivery via ingested lipid nanoparticles bioencapsulated within plant cell-based enfolding

2019 ◽  
Author(s):  
Tatiana Hillman
Keyword(s):  
Dna Sequences ◽  
Genetic Disorders ◽  
Single Point ◽  
Lipid Nanoparticles ◽  
Target Cells ◽  
Single Point Mutation ◽  
Cas9 Nuclease ◽  
Target Dna ◽  
Sgrna Design

The possibility of gene editing to correct disorders is one of the most impactful therapeutic agents, currently. CRISPR Cas9-sgRNA nucleases can be used to cleave and to delete harmful or pathogenic DNA sequences, which cause genetic disorders. Cas9 nuclease with palindromic repeats can cut and delete a single point mutation or multiple DNA target site sequences. The Cas9, attached to a sgRNA or a guiding RNA, finds and then cleaves the target DNA sequence. The Cas9-sgRNA method of cleavage has corrected DNA mutations that cause cataracts in the eyes, cystic fibrosis, and chronic granulomatous disease. However, there are issues for producing a less strenuous delivery of Cas9-sgRA to target DNA sequences. Delivering Cas-9 nucleases are negatively affected by off-target DNA sites, sgRNA design, off-target cleavage, Cas9 activation, and the method of delivery. This review focuses on oral and ingested delivery methods to effectively guide the transport of Cas9-sgRNA nucleases in vivo. A review of Cas9 delivery will present possible alternatives for nuclease delivery within optimized lipid-nanoparticles, plant, algae, and bacterial-based orally ingested edibles. This review will attempt to provide evidence in support of enhancing the Cas9 delivery through therapeutic bioencapsulated ingestion. In this review, it is suggested that the ingestion of encapsulated edibles carrying the nuclease can more directly target cells within the gastrointestinal tract for blood or lymph circulation.

scholarly journals A review: Possible optimization of Cas9-sgRNA nuclease delivery via ingested lipid nanoparticles bioencapsulated within plant cell-based enfolding

2019 ◽  
Author(s):  
Tatiana Hillman
Keyword(s):  
Dna Sequences ◽  
Genetic Disorders ◽  
Single Point ◽  
Lipid Nanoparticles ◽  
Target Cells ◽  
Single Point Mutation ◽  
Cas9 Nuclease ◽  
Target Dna ◽  
Sgrna Design

The possibility of gene editing to correct disorders is one of the most impactful therapeutic agents, currently. CRISPR Cas9-sgRNA nucleases can be used to cleave and to delete harmful or pathogenic DNA sequences, which cause genetic disorders. Cas9 nuclease with palindromic repeats can cut and delete a single point mutation or multiple DNA target site sequences. The Cas9, attached to a sgRNA or a guiding RNA, finds and then cleaves the target DNA sequence. The Cas9-sgRNA method of cleavage has corrected DNA mutations that cause cataracts in the eyes, cystic fibrosis, and chronic granulomatous disease. However, there are issues for producing a less strenuous delivery of Cas9-sgRA to target DNA sequences. Delivering Cas-9 nucleases are negatively affected by off-target DNA sites, sgRNA design, off-target cleavage, Cas9 activation, and the method of delivery. This review focuses on oral and ingested delivery methods to effectively guide the transport of Cas9-sgRNA nucleases in vivo. A review of Cas9 delivery will present possible alternatives for nuclease delivery within optimized lipid-nanoparticles, plant, algae, and bacterial-based orally ingested edibles. This review will attempt to provide evidence in support of enhancing the Cas9 delivery through therapeutic bioencapsulated ingestion. In this review, it is suggested that the ingestion of encapsulated edibles carrying the nuclease can more directly target cells within the gastrointestinal tract for blood or lymph circulation.

Pharmacokinetic Evaluation of 99mTc-radiolabeled Solid Lipid Nanoparticles and Chitosan Coated Solid Lipid Nanoparticles

2020 ◽  
Vol 20 (13) ◽  
pp. 1044-1052
Author(s):  
Nasrin Abbasi Gharibkandi ◽  
Sajjad Molavipordanjani ◽  
Jafar Akbari ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
High Resistivity ◽  
Scanning Calorimetry ◽  
Liver Uptake ◽  
Solid Lipid ◽  
Transmission Electron ◽  
Main Portion ◽  
Pharmacokinetic Behavior

Background: Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of 99mTc-labeled SLNs and chitosan modified SLNs in mice. Methods: 99mTc-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (99mTc-SLNs) and radiolabeled chitosan-coated SLNs (99mTc-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS). Results: 99mTc-oxine with high radiochemical purity (RCP~100%) and stability (RCP > 97% at 24 h) was used to provide 99mTc-SLNs and 99mTc-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest 99mTc- SLNs susceptibility to aggregation. To that end, the main portion of 99mTc-SLNs radioactivity accumulates in the liver and intestines, while 99mTc-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of 99mTc-Chi-SLNs was higher than that of 99mTc-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. 99mTc- Chi-SLNs uptake in the kidneys in comparison with 99mTc-SLNs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h. Conclusion: The chitosan layer on the surface of 99mTc-Chi-SLNs reduces lipophilicity in comparison with 99mTc- SLNs. Therefore, 99mTc-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration.

Solid Lipid Nanoparticles (SLNs) Gels for Topical Delivery of Aceclofenac in vitro and in vivo Evaluation

2013 ◽  
Vol 10 (6) ◽  
pp. 656-666 ◽  
Author(s):  
Sandipan Dasgupta ◽  
Surajit Ghosh ◽  
Subhabrata Ray ◽  
Bhaskar Mazumder
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Topical Delivery ◽  
Lipid Nanoparticles ◽  
In Vivo Evaluation ◽  
Solid Lipid

scholarly journals Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver

2021 ◽  
Vol 7 (9) ◽  
pp. eabf4398
Author(s):  
M. Kim ◽  
M. Jeong ◽  
S. Hur ◽  
Y. Cho ◽  
J. Park ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Targeted Delivery ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Nanoparticles ◽  
Liver Sinusoidal Endothelial Cells ◽  
Main Challenge ◽  
Cell Type Specific ◽  
Selective Delivery

Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol–lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type–specific delivery of RNA into the liver and other tissues.

scholarly journals Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo

2012 ◽  
Vol 124 (34) ◽  
pp. 8657-8661 ◽  
Author(s):  
Muthusamy Jayaraman ◽  
Steven M. Ansell ◽  
Barbara L. Mui ◽  
Ying K. Tam ◽  
Jianxin Chen ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Lipid Nanoparticles
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