Method for characterizing molecule delivery particles

1 . A method for characterizing a molecule delivery particle, wherein the first particle comprises a first coat and a first delivery molecule, and the second particle comprises a second coat; the method comprising:

subjecting a molecule delivery particle comprising a first particle and a second particle to particle separation with optical measurement to determine an increment in refractive index of each of the first particle and the second particle; and

determining a molar concentration of each of the first particle and the second particle based on the increment in refractive index, a molecular weight, and a specific refractive index increment of each of the first particle and the second particle;

wherein the method comprises:

subjecting the molecule delivery particle to particle separation with optical measurement at a plurality of measurement wavelengths to determine an absorbance of each of the first particle and the second particle for each measurement wavelength of the plurality of measurement wavelengths; and

determining a molar extinction coefficient of each of the first particle and the second particle for the each measurement wavelength based on the absorbance of each of the first particle and the second particle and the molar concentration of each of the first particle and the second particle;

and the method comprises:

determining a molar extinction coefficient of the first particle and the second particle for the each measurement wavelength based on the absorbance of each of the first particle and the second particle and the molar concentration of each of the first particle and the second particle; and

determining a molar extinction coefficient of the first delivery molecule for the each measurement wavelength by subtracting the molar extinction coefficient of the second particle from the molar extinction coefficient of the first particle.

2 . The method according to claim 1 , wherein the method comprises:

identifying an isosbestic point at which the molar extinction coefficient of the second particle and the molar extinction coefficient of the first delivery molecule are consistent with each other; and

determining a quantitative ratio between the first particle and the second particle by using the absorbance of each of the first particle and the second particle at the isosbestic point.

3 . The method according to claim 2 , wherein the method comprises determining that the molecule delivery particle has a predetermined quality when the quantitative ratio exceeds a first threshold.

4 . The method according to claim 1 , wherein the molecule delivery particle further comprises a third particle, and the third particle comprises a third coat and optionally comprises a third delivery molecule; and

the method comprises:

determining an absorbance of the third particle for the each measurement wavelength by particle separation with optical measurement of the molecule delivery particle; and

determining a degree of contribution of the molar extinction coefficient of the second particle and the molar extinction coefficient of the first delivery molecule to the absorbance of the third particle.

5 . The method according to claim 4 , wherein the method further comprises: determining a proportion of the third particle; and/or determining a concentration of each of the third coat and the third delivery molecule, based on the degree of contribution.

6 . The method according to claim 5 , wherein the method comprises determining a quantitative ratio of the first particle or the second particle to the molecule delivery particle based on the molar concentration of the first particle, the molar concentration of the second particle, the concentration of the third coat, and the concentration of the third delivery molecule, and determining that the molecule delivery particle has a predetermined quality when the quantitative ratio exceeds a first threshold.

7 . The method according to claim 1 , wherein the particle separation is centrifugation, chromatography, or field flow fractionation.

8 . The method according to claim 1 , wherein the molecule delivery particle is a virus particle, a liposome, an albumin particle, a micelle, or a polylactic acid-glycolic acid copolymer particle.

9 . The method according to claim 8 , wherein the virus particle is an adeno-associated virus, an adenovirus, a herpes virus, a Sendai virus, a stealth virus, a lentivirus, or a retrovirus.

10 . A program that, when loaded into a control unit of a computer, causes the computer to execute the method according to claim 1 .