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Polyamino acid for targeted delivery of mRNA vaccine and preparation method and application of polyamino acid

A polyamino acid and amino acid technology, applied in the field of polymer materials, can solve the problems of inability to achieve effective delivery of mRNA vaccines and drugs, and low delivery efficiency, and achieve good biocompatibility and targeted delivery efficiency

Pending Publication Date: 2021-12-14
天津力博生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the existence of "lysosomal traps", the delivery efficiency of existing delivery systems is very low, and the effective delivery of mRNA vaccines and drugs cannot be achieved

Method used

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  • Polyamino acid for targeted delivery of mRNA vaccine and preparation method and application of polyamino acid
  • Polyamino acid for targeted delivery of mRNA vaccine and preparation method and application of polyamino acid
  • Polyamino acid for targeted delivery of mRNA vaccine and preparation method and application of polyamino acid

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preparation example Construction

[0131] The preparation method of the present invention will be further described in detail in conjunction with specific examples below. It should be understood that the following examples are only for illustrating and explaining the present invention, and should not be construed as limiting the protection scope of the present invention. All technologies realized based on the above contents of the present invention are covered within the scope of protection intended by the present invention.

[0132] The experimental methods used in the following examples are conventional methods unless otherwise specified; the reagents and materials used in the following examples can be obtained from commercial sources unless otherwise specified.

[0133] The buffer solution used in the following examples is a commonly used buffer solution, including phosphate buffer solution, HEPES buffer solution and Tris buffer solution, and the water is MiliQ deionized water after autoclave sterilization, ...

Embodiment 1

[0136] Example 1 Preparation of polyamino acid PLL-SSMO25-PEG2000-Biotin20

[0137] Weigh 10 mg of α-poly-L-lysine hydrobromide (hydrobromide of PLL, average molecular weight 22,500 Daltons), and dissolve it in 150 µL of phosphate buffer (pH 7.4) to obtain a solution ( A). Weigh 20 mg of polyethylene glycol 2000 (BIOTIN-PEG2000-SCM, polyethylene glycol with an average molecular weight of 2000 Daltons) modified with biotin and succinimide carboxymethyl ester, purchased from Beijing Jiankai Technology Co., Ltd. company), which was dissolved in 150 µL tetrahydrofuran (analytical grade, Nanjing Reagent Company). To the resulting solution was added 3.8 mg of succinimide 3-(2-pyridyldithio)propionate (SPDP, molecular weight 312, Thermo Fisher) coupling agent to obtain a mixture solution (B). Mix solution (A) and solution (B) in a test tube, shake and react at room temperature for 4 hours, then add 1.2 times the reaction equivalent of n-octyl mercaptan 2.5 µL (MO, analytical grade,...

Embodiment 2

[0140] Example 2 Preparation of polyamino acid PLL-SSMO25-PEG3500-Biotin20

[0141]Weigh 10 mg of PLL hydrobromide (average molecular weight 22,500 Daltons) in a 2 mL centrifuge tube and dissolve it in 150 µL of phosphate buffer (pH 7.4) to obtain solution (A). Weigh 33 mg of polyethylene glycol 3500 (BIOTIN-PEG3500-SCM, polyethylene glycol with an average molecular weight of 3500 Daltons) modified with biotin and succinimide carboxymethyl ester, purchased from Beijing Jiankai Technology Co., Ltd. company), dissolved in 150 µL THF. To the resulting solution was added 3.8 mg of succinimide 3-(2-pyridyldithio)propionate (SPDP, molecular weight 312, Thermo Fisher) coupling agent to obtain a mixture solution (B). Mix solution (A) and solution (B) in a test tube, shake and react at room temperature for 4 hours, then add 1.2 times the reaction equivalent of n-octyl mercaptan 2.5 µL (MO, analytical grade, molecular weight 146, density 0.84 g / L, Beijing Bailingwei Company). The rea...

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Abstract

The invention provides polyamino acid for targeted delivery of a mRNA vaccine and a preparation method and application of the polyamino acid. The polyamino acid is side-chain-modified polyamino acid; a hydrophilic component and a hydrophobic component are introduced into the side chain of the polyamino acid, so polyamino acid micelles can be formed, and the micelles are used for efficiently delivering nucleic acid molecules. According to the side-chain-modified polyamino acid disclosed by the invention, a disulfide bond split in a reducing environment is introduced on the side chain, so the response of micelles to the reducing environment and a low pH value in cytoplasm can be promoted, and the mRNA vaccine is helped to actively escape from a lysosome trap and enter the cytoplasm. The active cleavage of a nanocarrier can more efficiently release mRNA compared to a passive osmotic pressure dominated escape process.

Description

technical field [0001] The invention belongs to the field of polymer materials, and relates to a polyamino acid for targeted delivery of mRNA vaccines, a preparation method and application thereof. Background technique [0002] Viruses are a major public health security threat to human health. The use of vaccines is an effective means for humans to fight against viruses. Since the smallpox virus was defeated by inoculation of "vaccinia", vaccines have helped humans effectively control and prevent diseases caused by many viruses, including hepatitis A virus, hepatitis B virus, meningitis B and influenza virus. The development of vaccines against the deadly Ebola virus and coronaviruses causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) has become a key factor in controlling viral infection outbreaks urgent needs. According to different technical routes, the types of vaccines include inactivated...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00C08G69/48C08G69/10A61K47/64A61K47/60A61K9/107A61K48/00A61K31/7088A61K39/00A61P31/00A61P35/00A61P17/00A61P39/06
CPCC08G81/00C08G69/48C08G69/10A61K47/645A61K47/60A61K9/1075A61K48/005A61K48/0041A61K31/7088A61K39/00A61P31/00A61P35/00A61P17/00A61P39/06A61K2039/53
Inventor 王海龙
Owner 天津力博生物科技有限公司
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