CN103052400B - 自我复制rna分子的病毒样递送颗粒 - Google Patents
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Abstract
Description
2周 | 4周 | 8周 | |
0.1μg | 2.9 | 1.0 | 1.1 |
1μg | 2.3 | 0.9 | 0.9 |
RV | Zav(nm) | pdI | 包封率% | 方法 |
RV01(10) | 158.6 | 0.088 | 90.7 | (A) |
RV01(08) | 156.8 | 0.144 | 88.6 | (A) |
RV01(05) | 136.5 | 0.136 | 99 | (B) |
RV01(09) | 153.2 | 0.067 | 76.7 | (A) |
RV01(10) | 134.7 | 0.147 | 87.8* | (A) |
RV13(02) | 128.3 | 0.179 | 97 | (A) |
RV | 第14天 | 第36天 |
裸DNA质粒 | 439 | 6712 |
裸A317RNA | 78 | 2291 |
RV01(10) | 3020 | 26170 |
RV01(08) | 2326 | 9720 |
RV01(05) | 5352 | 54907 |
RV01(09) | 4428 | 51316 |
RV01(10)DNA | 5 | 13 |
RV13(02) | 644 | 3616 |
RNA | 颗粒大小Zav(nm) | 多分散度 | RNA包封率 |
vA317 | 155.7 | 0.113 | 86.6% |
vA17 | 148.4 | 0.139 | 92% |
vA336 | 145.1 | 0.143 | 92.9% |
空白 | 147.9 | 0.147 | - |
天数 | 1 | 2 | 3 | 4 | - |
14 | 22 | 1819 | 5 | 5 | 5 |
35 | 290 | 32533 | 9 | 19877 | 5 |
51 | 463 | 30511 | 18 | 20853 | 5 |
天数 | 1 | 2 | 3 | 4 |
51 | 35 | 50 | 24 | 38 |
细胞因子 | 1 | 2 | 3 | 4 |
IFN-γ | 0.04 | |||
IL2 | 0.02 | 0.06 | 0.02 | |
IL5 | ||||
TNFα | 0.03 | 0.05 |
细胞因子 | 1 | 2 | 3 | 4 |
IFN-γ | 0.37 | 0.87 | ||
IL2 | 0.11 | 0.40 | 0.04 | |
IL5 | ||||
TNFα | 0.29 | 0.79 | 0.06 |
A | - | - |
B | 0.1μg of(i),裸露 | - |
C | 0.1μg of(i),包封在脂质体内 | - |
D | 0.1μg of(i),和分离脂质体 | - |
E | 0.1μg of(i),裸露 | 10μg of(ii),裸露 |
F | 0.1μg of(i),裸露 | 10μg of(iii),裸露 |
G | 0.1μg of(i),包封在脂质体内 | 10μg of(ii),裸露 |
H | 0.1μg of(i),包封在脂质体内 | 10μg of(iii),裸露 |
I | 0.1μg of(i),包封在脂质体内 | 1μg of(ii),包封在脂质体内 |
J | 0.1μg of(i),包封在脂质体内 | 1μg of(iii),包封在脂质体内 |
K | 5μg F蛋白 | - |
L | 5μg F蛋白 | 1μg of(ii),包封在脂质体内 |
M | 5μg F蛋白 | 1μg of(iii),包封在脂质体内 |
天数 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
14 | 82 | 2463 | 789 | 2496 | 1171 | 1295 | 1293 | 5 |
35 | 1538 | 34181 | 25605 | 23579 | 13718 | 8887 | 73809 | 5 |
IgG | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
IgG1 | 94 | 6238 | 4836 | 7425 | 8288 | 1817 | 78604 |
IgG2a | 5386 | 77064 | 59084 | 33749 | 14437 | 17624 | 24 |
天数 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
35 | <20 | 143 | 20 | 101 | 32 | 30 | 111 | <20 |
49 | <20 | 139 | <20 | 83 | 41 | 32 | 1009 | <20 |
天数 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
14 | 1140 | 2133 | 1026 | 2792 | 3045 | 1330 | 2975 | 5 | 1101 |
35 | 1721 | 5532 | 3184 | 3882 | 9525 | 2409 | 39251 | 5 | 12139 |
IgG | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
IgG1 | 66 | 247 | 14 | 328 | 468 | 92 | 56258 | 79 |
IgG2a | 2170 | 7685 | 5055 | 6161 | 1573 | 2944 | 35 | 14229 |
天数 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
35 | <20 | 27 | 29 | 22 | 36 | <20 | 28 | <20 | <20 |
49 | <20 | 44 | 30 | 23 | 36 | <20 | 33 | <20 | 37 |
天数 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
14 | 5 | 2049 | 1666 | 1102 | 298 | 984 | 3519 | 5 | 806 |
35 | 152 | 27754 | 19008 | 17693 | 3424 | 6100 | 62297 | 5 | 17249 |
IgG | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
IgG1 | 5 | 1323 | 170 | 211 | 136 | 34 | 83114 | 189 |
IgG2a | 302 | 136941 | 78424 | 67385 | 15667 | 27085 | 3800 | 72727 |
天数 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
35 | <20 | 539 | 260 | 65 | 101 | 95 | 443 | <20 | 595 |
49 | <20 | 456 | 296 | 35 | 82 | 125 | 1148 | <20 | 387 |
gH/gL VRP | gHsol/gL VRP | gH/gL脂质体 | gHsol/gL脂质体 |
4576 | 2393 | 4240 | 10062 |
疫苗组别 | 3wp1 | 3wp2 | 3wp3 |
1 | 126 | 6296 | 26525 |
2 | N/A | N/A | 6769 |
3 | N/A | 3442 | 7348 |
4 | N/A | N/A | 2265 |
5 | 347 | 9848 | 42319 |
6 | 179 | 12210 | 80000 |
7 | 1510 | 51200 | 130000 |
8 | N/A | N/A | 845 |
9 | N/A | N/A | 228 |
10 | N/A | N/A | 413 |
天数 | 1 | 2 | 3 | 4 |
14 | 42 | 21 | 2669 | 2610 |
35 | 241 | 154 | 17655 | 18516 |
天数 | 1 | 2 | 3 | 4 | 5 |
3 | 8.69E+07 | 3.33E+06 | 2.11E+06 | 9.71E+06 | 1.46E+07 |
7 | 1.04E+08 | 8.14E+06 | 1.83E+07 | 5.94E+07 | 1.64E+07 |
14 | 8.16E+07 | 2.91E+06 | 9.22E+06 | 3.48E+07 | 8.49E+05 |
21 | 1.27E+07 | 3.13E+05 | 6.79E+04 | 5.07E+05 | 6.79E+05 |
28 | 1.42E+07 | 6.37E+05 | 2.36E+04 | 4.06E+03 | 2.00E+03 |
35 | 1.21E+07 | 6.12E+05 | 2.08E+03 | ||
42 | 1.49E+07 | 8.70E+05 | |||
49 | 1.17E+07 | 2.04E+05 | |||
63 | 9.69E+06 | 1.72E+03 | |||
70 | 9.29E+06 |
Claims (11)
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DK3243526T3 (da) | 2010-07-06 | 2020-02-17 | Glaxosmithkline Biologicals Sa | Levering af rna til at udløse flere immunsignalveje |
CN106421773A (zh) | 2010-07-06 | 2017-02-22 | 诺华股份有限公司 | 自我复制rna分子的病毒样递送颗粒 |
CA3169291A1 (en) | 2010-07-06 | 2012-01-12 | Glaxosmithkline Biologicals Sa | Immunisation of large mammals with low doses of rna |
CN108042799A (zh) | 2010-07-06 | 2018-05-18 | 诺华股份有限公司 | 阳离子水包油乳液 |
EP2590626B1 (en) | 2010-07-06 | 2015-10-28 | GlaxoSmithKline Biologicals SA | Liposomes with lipids having an advantageous pka-value for rna delivery |
WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
HRP20221533T1 (hr) | 2010-08-31 | 2023-02-17 | Glaxosmithkline Biologicals Sa | Pegilirani liposomi za isporuku rna koja kodira imunogen |
SI4008357T1 (sl) | 2010-08-31 | 2023-04-28 | Glaxosmithkline Biologicals Sa | Mali liposomi za dostavo imunogen-kodirajoče RNA |
DK3590949T3 (da) | 2010-10-01 | 2022-07-11 | Modernatx Inc | Ribonukleinsyrer indeholdende n1-methyl-pseudouracil og anvendelse heraf |
MX363307B (es) * | 2010-10-11 | 2019-03-20 | Novartis Ag Star | Plataformas para suministro de antigenos. |
US8710200B2 (en) | 2011-03-31 | 2014-04-29 | Moderna Therapeutics, Inc. | Engineered nucleic acids encoding a modified erythropoietin and their expression |
CA3107288A1 (en) | 2011-06-08 | 2012-12-13 | Translate Bio, Inc. | Lipid nanoparticle compositions and methods for mrna delivery |
JP2014520806A (ja) * | 2011-07-06 | 2014-08-25 | ノバルティス アーゲー | Rna分子の送達のための有用なn:p比を有するリポソーム |
WO2013006837A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Cationic oil-in-water emulsions |
EP3424495A1 (en) | 2011-07-06 | 2019-01-09 | GlaxoSmithKline Biologicals S.A. | Oil-in-water emulsions that contain nucleic acids |
EP2729165B1 (en) | 2011-07-06 | 2017-11-08 | GlaxoSmithKline Biologicals SA | Immunogenic combination compositions and uses thereof |
AU2012301715B2 (en) * | 2011-08-31 | 2017-08-24 | Glaxosmithkline Biologicals S.A. | Pegylated liposomes for delivery of immunogen-encoding RNA |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
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