siRNA against KIR3DL1 as a potential gene therapeutic agent in controlling HIV-1 infection.
OBJECTIVE
The aim of this study was to develop a small interfering RNA (siRNA) against the expression of KIR3DL1 receptor on natural killer (NK) cells, in order to promote the ability of NK cells to destroy human immunodeficiency virus (HIV)-infected cells and thus prevent failure of siRNA therapy targeting human immunodeficiency virus type 1 (HIV-1) virus among HIV-1 infected patients in vitro.


METHODS
A siRNA targeting KIR3DL1 was synthesized and then modified with cholesterol, methylene, and sulfate. The inhibitory action of the siRNAs on primary cultured NK cells was detected. The amount of IFN-γ and TNF-α secretions in NK cells was measured. The intended functions of NK cells in vitro were analyzed by CFSE and PI methods.


RESULTS
There were no significant differences in inhibiting the expression of KIR3DL1 on NK cells between the modified and unmodified siRNAs, while inhibition by each of them differed significantly from controls. The amount of IFN-γ and TNF-α secretions in the NK cells was abundant due to unsuccessful expression of KIR3DL1 on NK cells, which further promoted function of the NK cells.


CONCLUSIONS
The siRNA against KIR3DL1 could enhance the ability of the NK cells to kill the HIV-1 infected cells in vitro and successfully prevented the failure of siRNA therapy targeting the HIV-1 virus. Therefore, it can act as a potential gene therapeutic agent among HIV-1 infected people.
1 Jiangsu Provincial Center for Disease Prevention and Control , Nanjing, China .
Geng-Feng
GF
Fu
Ji-Cheng
JC
Pan
Nan
N
Lin
Hai-Yang
HY
Hu
Wei-Ming
WM
Tang
Jin-Shui
JS
Xu
Xiao-Liang
XL
Wang
Xiao-Qin
XQ
Xu
Tao
T
Qiu
Xiao-Yan
XY
Liu
Guo-Hong
GH
Chen
Tanmay
T
Mahapatra
Xi-Ping
XP
Huan
Hai-Tao
HT
Yang
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D015658:HIV Infections / Q000628:therapy; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D054341:Receptors, KIR3DL1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007155:Immunologic Factors; C515083:KIR3DL1 protein, human; D034741:RNA, Small Interfering; D054341:Receptors, KIR3DL1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma