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Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing
Li, Bowen ; Manan, Rajith Singh ; Liang, Shun-Qing , et al. Nat. Biotechnol.,2023,41(10):1410-1415. DOI: 10.1038/s41587-023-01679-x PubMed ID: 36997680
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Abstract: The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of biodegradable ionizable lipids to build inhalable delivery vehicles for mRNA and CRISPR-Cas9 gene editors. Lead lipid nanoparticles are amenable for repeated intratracheal dosing and could achieve efficient gene editing in lung epithelium, providing avenues for gene therapy of congenital lung diseases.
Purchased from AmBeed: 14916-80-4 ; 294-90-6 ; 13093-04-4 ; 65604-89-9 ; 22366-98-9 ; 143-28-2 ; 1484-84-0 ; 112-92-5 ; 3433-37-2 ; 34803-66-2 ; 622-26-4 ; 934-98-5 ; 3529-08-6 ; 123-70-6 ; 23356-96-9 ; 534-26-9 ; 4730-54-5 ; 108-00-9 ; 51388-00-2 ; 6711-48-4 ; 506-43-4 ; 2038-03-1 ; 142-25-6 ; 27578-60-5 ; 67980-77-2 ; 4572-03-6 ; 14156-95-7 ; 10563-26-5 ; 4097-88-5 ; 111-33-1 ; 123-12-6 ; 6261-22-9 ; 496808-04-9 ; 3644-18-6 ; 764-60-3 ; 1002-36-4 ; 51-45-6 ; 112086-54-1 ; 22104-79-6 ; 67529-83-3 ; 10563-29-8 ; 294-90-6 ; 506-43-4 ; 20739-58-6 ; 13901-38-7 ; 938459-02-0 ; 7209-38-3 ; 51721-39-2 ; 18128-28-4 ; 105-83-9 ; 877-96-3 ; 14712-23-3 ; 915922-79-1 ; 205059-32-1 ; 5298-72-6 ; 22763-69-5 ...More
CAS No. : | 4730-54-5 | MDL No. : | MFCD00012358 |
Formula : | C6H15N3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ITWBWJFEJCHKSN-UHFFFAOYSA-N |
M.W : | 129.20 | Pubchem ID : | 188318 |
Synonyms : |
1,4,7-Triazacyclononane
|
Chemical Name : | 1,4,7-Triazacyclononane |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P501-P260-P264-P280-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P405 | UN#: | 3259 |
Hazard Statements: | H314 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.31% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 25℃;Cooling with ice; | To a solution of 1,4,7-triazonane (1.00 g, 7.74 mmol) in DCM (30 mL) was added DIEA (3.00 g, 23.2 mmol, 4.04 mL) in an ice-bath (0 C.) and followed by addition of <strong>[6608-47-5]ethenesulfonyl chloride</strong> (2.94 g, 23.2 mmol, 2.28 mL). Then the mixture was warmed slowly to 25 C. and stirred for 4 hr. LC-MS showed starting material was consumed completely and desired mass was detected. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition) to give the desired product (300 mg, 9.31%) as a white solid. 1H NMR: CDCl3delta 10.79 (s, 1H), 7.27 (s, 2H), 6.49-6.59 (m, 3H), 6.30 (s, 1H), 6.26 (s, 1H), 6.24-6.33 (m, 1H), 6.04-6.09 (m, 1H), 6.05 (s, 1H), 6.03-6.06 (m, 1H), 3.47 (s, 12H) Purity by LC-MS: 95.10%, RT: 1.46 |
A1369652[ 1185291-73-9 ]
1,4,7-Triazonane hydrochloride
Reason: Free-salt