PMID- 35297601
OWN - NLM
STAT- MEDLINE
DCOM- 20220419
LR  - 20220605
IS  - 2576-6422 (Electronic)
IS  - 2576-6422 (Linking)
VI  - 5
IP  - 4
DP  - 2022 Apr 18
TI  - Influence of Hydrophobicity in the Hydrophilic Region of Cationic Lipids on 
      Enhancing Nucleic Acid Delivery and Gene Editing.
PG  - 1489-1500
LID - 10.1021/acsabm.1c01226 [doi]
AB  - Intracellular delivery of biomolecules using non-viral vectors critically depends 
      on the vectors' ability to allow the escape and release of the contents from the 
      endosomes. Prior findings demonstrated that aromatic/hydrophobic group-containing 
      amino acids such as phenylalanine (F) and tryptophan (W) destabilize cellular 
      membranes by forming pores in the lipid bilayer. Taking cues from these findings, 
      we have developed four alpha-tocopherol-based cationic amphiphiles by varying the 
      aromatic/hydrophobic amino acids such as glycine (G), proline (P), phenylalanine 
      (F), and tryptophan (W) as head groups and triazole in the linker region to study 
      their impact on endosomal escape for the enhanced transfection efficacy. The 
      lipids tocopherol-triazole-phenylalanine (TTF) and tocopherol-triazole-tryptophan 
      (TTW) exhibited similar potential to commercial transfecting reagents, 
      Lipofectamine (LF) 3000 and Lipofectamine Messenger Max (LFMM), respectively, in 
      transfecting plasmid DNA and messenger RNA in multiple cultured cell lines. The 
      TTW liposome was also found to be effective in delivering Cas9 mRNA and 
      demonstrated equal efficiency of gene editing AAVS1 locus compared to LFMM in 
      CHO, Neuro-2a, and EA.HY926 cell lines. In this current investigation, it is 
      shown that the synthesized cationic lipids with aromatic hydrophobic R 
      group-containing amino acids are safe, economic, and actually more efficient in 
      nucleic acid delivery and genome-editing applications. These findings can be 
      further explored in the genome-editing approach for treating genetic disorders.
FAU - Rapaka, Hithavani
AU  - Rapaka H
AD  - National Institute of Technology Warangal, Warangal, Telangana 506004, India.
FAU - Manturthi, Shireesha
AU  - Manturthi S
AD  - National Institute of Technology Warangal, Warangal, Telangana 506004, India.
FAU - Arjunan, Porkizhi
AU  - Arjunan P
AD  - Christian Medical College, Centre for Stem Cell Research, Vellore, Tamilnadu 
      632001, India.
FAU - Venkatesan, Vigneshwaran
AU  - Venkatesan V
AD  - Christian Medical College, Centre for Stem Cell Research, Vellore, Tamilnadu 
      632001, India.
FAU - Thangavel, Saravanabhavan
AU  - Thangavel S
AD  - Christian Medical College, Centre for Stem Cell Research, Vellore, Tamilnadu 
      632001, India.
FAU - Marepally, Srujan
AU  - Marepally S
AD  - Christian Medical College, Centre for Stem Cell Research, Vellore, Tamilnadu 
      632001, India.
FAU - Patri, Srilakshmi V
AU  - Patri SV
AUID- ORCID: 0000-0002-2104-0007
AD  - National Institute of Technology Warangal, Warangal, Telangana 506004, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220317
PL  - United States
TA  - ACS Appl Bio Mater
JT  - ACS applied bio materials
JID - 101729147
RN  - 0 (Amino Acids)
RN  - 0 (Cations)
RN  - 0 (Lipids)
RN  - 0 (Nucleic Acids)
RN  - 0 (Triazoles)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 8DUH1N11BX (Tryptophan)
RN  - H4N855PNZ1 (alpha-Tocopherol)
SB  - IM
MH  - Amino Acids/chemistry
MH  - Cations/chemistry
MH  - Gene Editing
MH  - Gene Transfer Techniques
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Lipids/chemistry
MH  - *Nucleic Acids
MH  - Phenylalanine
MH  - Triazoles
MH  - Tryptophan
MH  - alpha-Tocopherol/chemistry
OTO - NOTNLM
OT  - cationic lipids
OT  - endosomal escape
OT  - gene editing
OT  - non-viral nucleic acid delivery
OT  - alpha-tocopherol
EDAT- 2022/03/18 06:00
MHDA- 2022/04/20 06:00
CRDT- 2022/03/17 12:11
PHST- 2022/03/18 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
PHST- 2022/03/17 12:11 [entrez]
AID - 10.1021/acsabm.1c01226 [doi]
PST - ppublish
SO  - ACS Appl Bio Mater. 2022 Apr 18;5(4):1489-1500. doi: 10.1021/acsabm.1c01226. Epub 
      2022 Mar 17.