期刊
ADVANCED FUNCTIONAL MATERIALS
卷 23, 期 9, 页码 1172-1181出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201102963
关键词
sleeping beauty transposon; phage display; mesenchymal stem cells; liposome; nuclear localization signal
类别
资金
- National Institutes of Health [R01HL092526-01A2, R03AR056848-01, 1R21EB015190-01A1, 5R01DE01563309]
- National Science Foundation [CBET-0854465, CBET-0854414, CBET-1229309, DMR-0847758]
- Oklahoma Center for Adult Stem Cell Research [434003]
- Oklahoma Center for the Advancement of Science and Technology [HR11-006]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0854465] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [847758] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0854414] Funding Source: National Science Foundation
- EPSCoR
- Office Of The Director [1158862] Funding Source: National Science Foundation
An important criterion for effective gene therapy is sufficient chromosomal integration activity. The Sleeping Beauty (SB) transposon system is a plasmid system allowing efficient insertion of transgenes into the host genome. However, such efficient insertion occurs only after the system is delivered to nuclei. Since transposons do not have the transducing abilities of viral vectors, efficient delivery of this system first into cells and then into cell nuclei is still a challenge. Here, a phage display technique using a major coat displayed phage library is employed to identify a peptide (VTAMEPGQ) that can home to rat mesenchymal stem cells (rMSCs). A nanoparticle, called liposome protamine/DNA lipoplex (LPD), is electrostatically assembled from cationic liposomes and an anionic complex of protamine, DNA and targeting peptides. Various peptides are enveloped inside the LPD to improve its targeting capability for rMSCs and nuclei. The rMSC-targeting peptide and nuclear localization signal (NLS) peptide can execute the synergetic effect to promote transfection action of LPD. The homing peptide directs the LPD to target the MSCs, whereas the NLS peptide directs transposon to accumulate into nuclei once LPD is internalized inside the cells, leading to increased gene expression. This suggests that rMSC-targeting peptide and NLS peptide within LPD can target to rMSCs and then guide transposon into nuclei. After entering the nuclei, SB transposon increase the insertion rates into cellular chromosomes. The targeting LPD does not show obvious cell toxicity and influence on the differentiation potential of rMSCs. Therefore, the integration of SB transposon and LPD system is a promising nonviral gene delivery vector in stem cell therapy.
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