CN107029218A - The purposes of acetylcholinesterase, butyrylcholine esterase or their mutant in preparing or screening the medicine for the treatment of tumour - Google Patents
The purposes of acetylcholinesterase, butyrylcholine esterase or their mutant in preparing or screening the medicine for the treatment of tumour Download PDFInfo
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- CN107029218A CN107029218A CN201610081079.4A CN201610081079A CN107029218A CN 107029218 A CN107029218 A CN 107029218A CN 201610081079 A CN201610081079 A CN 201610081079A CN 107029218 A CN107029218 A CN 107029218A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/01—Carboxylic ester hydrolases (3.1.1)
- C12Y301/01007—Acetylcholinesterase (3.1.1.7)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/01—Carboxylic ester hydrolases (3.1.1)
- C12Y301/01008—Cholinesterase (3.1.1.8), i.e. butyrylcholine-esterase
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Abstract
The present invention relates to biological technical field, the more particularly to purposes of acetylcholinesterase, butyrylcholine esterase or their mutant in preparing or screening the medicine for the treatment of tumour.Present invention offer acetylcholinesterase, the purposes of butyrylcholine esterase or their mutant in preparing or screening the medicine for the treatment of tumour, the medicine of the treatment tumour is oral administration medicine.The present invention utilizes the oral mode of acetylcholinesterase plasmid, butyrylcholine esterase plasmid, acetylcholinesterase, butyrylcholine esterase gene are free in outside animal Autosome and expressed, so as to improve security, convenience, and there is the effect of more preferable tumor prevention and treatment.Can see acetylcholinesterase, butyrylcholine esterase expression from cell in vitro and interior animal experiment has the effect of suppression to tumor cell lines such as non-small cell lung cancer, stomach cancer, liver cancer, breast cancer, colorectal cancer, prostate cancer, glioma, head and neck cancer, blood tumors.
Description
Technical field
The present invention relates to biological technical field, more particularly to acetylcholinesterase, butyrylcholine esterase or their mutant exists
The purposes in the medicine for the treatment of tumour is prepared or screens, the medicine of the treatment tumour is oral administration medicine.
Background technology
Since the eighties, all over the world, cancer research field numerous studies show enzyme acetylcholine enzyme (AChE) and BuCh ester
Enzyme (BChE) expression quantity reduction or activity reduction in cancer linked groups.Such as nervous system in various cancers, respiratory tract disappears
Change in road, liver, pancreas associated cancer and all decline with acetylcholinesterase expression quantity or activity reduction；Urogenital system such as kidney,
Bladder, uterine neck, ovary, breast, prostate cancer, skin, soft tissue and hematological system related neoplasms, AChE or BChE
Enzymatic activity or its gene structure function are defects；AChE in neoplastic hematologic disorder patient tissue, BChE enzymatic activitys are lower, and patient is pre-
It is poorer afterwards.
Research in recent years shows acetylcholine in addition to the function of neurotransmitter or a kind of endogenic growth hormone, acetylcholine by
The generation of overexpression or stirring effect the meeting induced cancer of body, in the cancer that smoking triggers especially significantly, this is carried this phenomenon
Show that we can trigger cancer by the undue stirring effect of acetylcholine too accumulation or acetylcholinergic receptor.
Acetylcholinesterase serves very important effect in the cyclic process of neurotransmitter acetylcholine, can hydrolyze rapidly
The acetylcholine accumulated in nerve synapse is so as to maintain normal neurotransmission function；The research in modern age shows that acetylcholinesterase is joined
With numerous cell functions, such as cell adhesion, cell differentiation and cell propagation；Acetylcholinesterase is a kind of Apoptosis
Mark, point out acetylcholinesterase may take part in the apoptosis of cell；Acetylcholine ester is reduced by way of clpp gene subtracts
Expression of enzymes can strengthen the anti-apoptotic and proliferation activity of tumour cell；The inhibitor of acetylcholinesterase can reduce Apoptosis and
Promote propagation, these results of study show that acetylcholinesterase serves very important work in the apoptosis and breeding of cell
With.Acetylcholinesterase is a tumor suppressor gene, and acetylcholinesterase is expressed in many cancer kind cell lines can suppress cancer cell
Propagation and apoptosis-induced.The formation of acetylcholinesterase apoptosis involvement corpusculum, 2004, Park et al. disclosed acetylcholine
Effect of the esterase in the forming process of apoptotic body.
True based on more than, Shen in 2008 et al. proposes that the reduction of acetylcholinesterase expression quantity or activity reduction cause acetylcholine to exist
Accumulation causes the dysequilibrium of microenvironment to be probably to cause the reason for cancer occurs in different tissues and organ.Therefore, by mending
The method balanced to reach prevention and treatment cancer for filling exogenous acetylcholinesterase to adjust acetylcholine is science and can
Checking.Acetylcholinesterase is expensive, and can only pass through intravenous injection；The present invention proposes that one kind utilizes chitosan nano
Particle reaches the method for prevention and treatment cancer by oral mode, price is just as the carrier of expression acetylcholinesterase
Preferably, the compliance of patient is improved by oral mode.
Have in the prior art and expressed acetylcholinesterase in animal body using virus, so as to play the role of suppression to tumour.
But exogenous gene expression is introduced by virus, it is necessary to restructuring insertion will be carried out in the chromosome of gene in animal body, so as to deposit
In destruction animal body autogene, or even trigger the possibility of animal oncogenic mutation.Meanwhile, it is viral as genophore,
The problems such as having many unsafe factors, such as immunogenicity, viral infectivity, viral recombinant.
The content of the invention
The shortcoming of prior art in view of the above, it is an object of the invention to provide acetylcholinesterase, butyrylcholine esterase or
Purposes of their mutant in preparing or screening the medicine for the treatment of tumour, the medicine of the treatment tumour is oral administration medicine,
For solving the problems of the prior art.
In order to achieve the above objects and other related objects, first aspect present invention provide acetylcholinesterase, butyrylcholine esterase or
Purposes of their mutant in preparing or screening the medicine for the treatment of tumour, the medicine of the treatment tumour is oral administration medicine.
Acetylcholinesterase, which is clinically shown with malignancy, very strong correlation, while also there is text in the prior art
Chapter shows that the effect of prevention and treatment tumour can be played by increasing acetylcholinesterase in vivo.But it is due to acetylcholinesterase egg
White extreme is unstable, so the mode of gene expression in vivo, which becomes, can uniquely increase the approach of protein content.In the prior art
Acetylcholinesterasegene gene is introduced in Mice Body by way of virus and the suppression of tumour is observed.But, virus because
The problems such as its infectivity, immunogenicity, recombinant, it is not a good genophore to be considered as.The present invention is by acetylcholine ester
Enzyme gene is cloned into expression vector, and by oral mode expressed in vivo there is provided one kind it is safer, easily
Administering mode.
In purposes provided by the present invention, one word for the treatment of is including that can cause the preventing property of the pharmacy and/or physiologic effect to be asked (i.e.,
It is preventative), the disposal of curative or retentivity.The effect preferably refers to medically reduce one or more symptoms or complete of tumour
It totally disappeared except (stage i.e. before clinical tumor performance) and/or reduction tumor development or deterioration occur for tumour, or retardance, delay tumour
Risk.
In purposes provided by the present invention, it is administered orally after referring to medicine by oral administration by intestines and stomach absorbed into serum, passes through blood circulation
Arrival is locally or systemically organized, and reaches the purpose for the treatment of disease.For oral drugs, drug absorption can start from oral cavity and stomach,
But most of by intestinal absorption, medicine must can enter general blood circulation by small bowel and liver.Medicine, which is administered orally, to be had
It is easy to use, low-cost the advantages of, generally also most safe.
Specifically, the mutant of the acetylcholinesterase refers to has more than 80% homology with acetylcholinesterase, preferably have
More than 90% homology, more preferably with more than 95% homology, and function or better than acetyl with acetylcholinesterase
The polypeptide of the function of cholinesterase.
Specifically, the mutant of the butyrylcholine esterase refers to has more than 80% homology with butyrylcholine esterase, preferably have
More than 90% homology, more preferably with more than 95% homology, and function or better than acetyl with butyrylcholine esterase
The polypeptide of the function of cholinesterase.
Because the activity of natural acetylcholinesterase cannot meet the complete regression of tumour on Partial tumors cell, so ability
Field technique personnel can carry out the screening of mutant to acetylcholinesterase, choose the higher mutant of activity, to obtain preferably
Tumor prevention and the effect suppressed.
In purposes provided by the present invention, the purposes is more specifically acetylcholinesterase, butyrylcholine esterase or their mutation
Purposes of the recombinant expression carrier of body in preparing or screening the medicine for the treatment of tumour.
The recombinant expression carrier of acetylcholinesterase, butyrylcholine esterase or their mutant is to include corresponding acetylcholine
The expression vector of esterase, butyrylcholine esterase or their mutant code sequence.The expression vector can select various be applied to
The expression vector of the gene expression of acetylcholinesterase, butyrylcholine esterase or their mutant.Specific expression applicatory is carried
Body includes but is not limited to eucaryon replication orgin, prokaryotic origin of replication such as promoter, the SV40/OriP such as CMV/PGK/EF-1
The non-integrating vectors (Episomal Plasmid) of (from pUC, pBR322 Ori etc.), such as pGS, pRcCMV.
Suitable carrier may be selected in those skilled in the art, or further carries out modification transformation to existing carrier, to build the acetyl
The recombinant expression carrier of cholinesterase, butyrylcholine esterase or their mutant, so as to obtain suitable for oral administration and energy
Enough reach the recombinant expression carrier of the acetylcholinesterase, butyrylcholine esterase or their mutant of desired expression.Institute
It can be higher protein expression level to state desired expression, to reach more preferable tumor inhibitory effect or one
Relatively reasonable protein expression level, to give rational dosage for Different Individual.
Specifically, the tumour is selected from non-small cell lung cancer, stomach cancer, liver cancer, breast cancer, colorectal cancer, prostate cancer, brain
The tumours such as glioma, head and neck cancer, blood tumor.
A kind of pharmaceutical composition of second aspect of the present invention offer, acetylcholinesterase of the described pharmaceutical composition including therapeutically effective amount,
The recombinant expression carrier of Acetylcholine esterase mutant, butyrylcholine esterase or butyrylcholine esterase mutant, the drug regimen
Thing is oral formulations.
Therapeutically effective amount corresponds to the purpose for the treatment of tumour, refers specifically to a consumption after during appropriate administration, can reach
Treat the effect to be asked of tumour.Herein, if it is " effective " that can reduce one or more symptom or clinical indices to represent the treatment
's.
More specifically, the medicine of the treatment tumour also includes pharmaceutically acceptable carrier.
Specifically, pharmaceutically acceptable carrier refers to the carrier for Therapeutic Administration, including various excipient and diluent.Should
Term refers to some such medicament carriers：Themselves it is not necessary active component, and does not have undue toxicity after administration.Close
Suitable carrier is well known to those of ordinary skill in the art.In Remington's Pharmaceutical Sciences (Mack
Pub.Co., N.J.1991) in can find discussing fully on pharmaceutically acceptable excipient.Pharmaceutically may be used in the composition
The carrier of receiving may include liquid, such as water, salt solution, glycerine and ethanol.In addition, there is likely to be in these carriers complementary
Material, such as disintegrant, wetting agent, emulsifying agent, pH buffer substance, algin, pectin, sodium carboxymethylcellulose (CMC),
Xanthans, gellan gum, guar gum, carragheen, sucrose, maltitol, steviol glycoside etc..
It is preferred that, the carrier is the various pharmaceutically acceptable carriers for being capable of the absorption of assist digestion road.Implement in the present invention one
In example, the pharmaceutically acceptable carrier is the PBS solution of chitosan solution, more specifically Quaternary Ammonium Salt of Chitosan.
In pharmaceutical composition provided by the present invention, the expression vector can select various suitable for acetylcholinesterase, butyryl courage
The expression vector of the gene expression of alkali esterase or their mutant.Specific expression vector applicatory includes but is not limited to carry
The promoters such as CMV/PGK/EF-1, SV40/OriP replication orgins etc., prokaryotic origin of replication (derive from pUC, pBR322 Ori
Deng) non-integrating vectors (Episomal Plasmid), such as pGS, pRcCMV.
Specifically, described pharmaceutical composition is used to treat tumour, the tumour is selected from non-small cell lung cancer, stomach cancer, liver cancer, breast
The tumours such as gland cancer, colorectal cancer, prostate cancer, glioma, head and neck cancer, blood tumor.
Third aspect present invention provides a kind for the treatment of method of tumour, by way of described pharmaceutical composition is administered orally
Individual is applied to, suppresses the propagation of tumour.
The individual refers to the animal (including mankind) of acceptable described pharmaceutical composition and/or treatment method, and hero is covered herein
Property with female two kinds of sexes, unless otherwise expressly specified.Therefore, it is described individual including at least any mammal, including but
It is not limited to：The mankind, inhuman primate, such as mammal, dog, cat, horse, sheep, pig, ox, it can be because utilizing
Pharmaceutical composition is stated to be treated and benefited.
Specifically, the tumour is selected from non-small cell lung cancer, stomach cancer, liver cancer, breast cancer, colorectal cancer, prostate cancer, brain
The tumours such as glioma, head and neck cancer, blood tumor.
The present invention is using the oral mode of acetylcholinesterase plasmid, butyrylcholine esterase plasmid, by acetylcholinesterase, butyryl
Ache gene is free in outside animal Autosome and expressed, so as to improve security, convenience, and has preferably swollen
The effect of knurl prevention and treatment.Acetylcholinesterase, butyrylcholine esterase table are can see from cell in vitro and interior animal experiment
Up to non-small cell lung cancer, stomach cancer, liver cancer, breast cancer, colorectal cancer, prostate cancer, glioma, head and neck cancer, blood
The tumor cell lines such as knurl have the effect of suppression.In addition, the present invention is further by introducing the active mutant of acetylcholinesterase,
Improve the activity of expressed acetylcholinesterase, thus substantially increase its in vitro growth of tumour cell suppress and dynamic in vivo
Drug effect in the experiment of thing core knurl.
Brief description of the drawings
Fig. 1 is shown as in the embodiment of the present invention 1 acetylcholinesterase to 12 plants of tumor cell line proliferation experiment schematic diagrames.
Fig. 2 is shown as in the embodiment of the present invention 2 butyrylcholine esterase to 5 plants of tumor cell line proliferation experiment schematic diagrames.
Fig. 3 is shown as acetylcholinesterase in the embodiment of the present invention 3/butyrylcholine esterase Tumor growth inhibition experiment schematic diagram.
Embodiment
Illustrate embodiments of the present invention below by way of specific instantiation, those skilled in the art can be as disclosed by this specification
Content understand easily the present invention other advantages and effect.The present invention can also add by way of a different and different embodiment
To implement or apply, the various details in this specification can also be based on different viewpoints and application, in the essence without departing from the present invention
God is lower to carry out various modifications or alterations.
Before the specific embodiment of the invention is further described, it should be appreciated that protection scope of the present invention is not limited to following specific
Specific embodiment；It is also understood that the term used in the embodiment of the present invention is to describe specific specific embodiment,
The protection domain being not intended to be limiting of the invention；In description of the invention and claims, unless clearly referred in addition in text
Go out, singulative " one ", " one " and " this " include plural form.
When embodiment provides number range, it should be appreciated that except non-invention is otherwise noted, two end points of each number range with
And any one numerical value can select between two end points.Unless otherwise defined, all technologies used in the present invention and section are academic
Language is identical with the meaning that those skilled in the art of the present technique are generally understood that.In addition to the specific method used in embodiment, equipment, material,
According to those skilled in the art to the grasp of prior art and the record of the present invention, it can also use and the embodiment of the present invention
Described in method, any method, equipment and the material of equipment, material similar or equivalent prior art realize the present invention.
Unless otherwise indicated, disclosed in this invention experimental method, detection method, preparation method using the art it is normal
Molecular biology, biochemistry, chromatin Structure and the analysis of rule, analytical chemistry, cell culture, recombinant DNA technology and phase
The routine techniques in pass field.These technologies existing perfect explanation in the prior art, for details, reference can be made to the MOLECULAR such as Sambrook
CLONING：A LABORATORY MANUAL, Second edition, Cold Spring Harbor Laboratory Press,
1989 and Third edition, 2001；Ausubel etc., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY,
John Wiley＆Sons, New York, 1987 and periodic updates；the series METHODS IN
ENZYMOLOGY, Academic Press, San Diego；Wolffe, CHROMATIN STRUCTURE AND FUNCTION,
Third edition, Academic Press, San Diego, 1998；METHODS IN ENZYMOLOGY, Vol.304,
Chromatin (P.M.Wassarman and A.P.Wolffe, eds.), Academic Press, San Diego, 1999；
With METHODS IN MOLECULAR BIOLOGY, Vol.119, Chromatin Protocols (P.B.Becker, ed.) Humana
Press, Totowa, 1999 etc..
Embodiment 1
Overexpression experiment of the acetylcholinesterase in tumor cell line：
By acetylcholinesterase-pGS carriers following cell line (U87MG, Cal27, A549, HepG2, MCF7,
MDA-MB-468, SW620, HT29, RKO, U373, K562, LNCap) middle overexpression, tested after 72 hours thin
Born of the same parents breed (Cell Titer Glo, Promega), calculate the suppression that acetylcholinesterase is overexpressed cell proliferation.By above-mentioned 12
Strain cell, according to 4000 cells/wells be inoculated in incubated overnight in 96 well culture plates (Cal27, RKO, SW620, LNCap,
K562 cell culture is in the hyclone of 1640 culture medium+10%, 5%CO2In incubator；U87MG、A549、HT29、
MCF7, U373, MDA-MB-468 cell culture are in the hyclone of DMEM high glucose mediums+10%, 5%CO2Incubator)；
AchE (transcript variant5 NM_001302622) (is passed through into PCR method by acetylcholinesterase-pGS carriers
After two sections connect HindIII and XbaI enzyme cutting site, acetylcholinesterase endonuclease bamhi is linked by the method for molecular cloning
To pGS carriers, AchE-pGS is built into) measured according to 300ng, 100ng, 30ng, 10ng per hole, pass through liposome transfection
(Lipofectimine3000, Life Technology) mode is transiently transfected into aim cell strain.After culture 72 hours, to
Culture plate adds the proliferative conditions that 50ul/ hole Cell Titer Glo detect cell, and concrete outcome is as shown in Figure 1.In Fig. 1, every four
In a kind of experimental result of cell line of individual column correspondence, each group column, from left to right four columns correspond to respectively 300ng,
The addition in 100ng, 30ng, 10ng acetylcholinesterase-pGS carriers/hole.
Embodiment 2
Overexpression experiment of the butyrylcholine esterase in tumor cell line：
By butyrylcholine esterase-pRcCMV carriers at following cell line (A549, Hela, HCT116, U87MG, RKO)
It is middle to be overexpressed, cell propagation (Cell Titer Glo, Promega) is detected after 48 hours, butyrylcholine esterase is calculated and is overexpressed to thin
The suppression of born of the same parents' propagation.By above-mentioned 5 plants of cells, according to 4000 cells/wells be inoculated in incubated overnight in 96 well culture plates (A549,
Hela, U87MG are cultivated in the hyclone of DMEM culture mediums+10%, 5%CO2 incubators；HCT116, RKO are thin
Born of the same parents are cultivated in the hyclone of 1640 culture medium+10%, 5%CO2 incubators), (will by butyrylcholine esterase-pRcCMV carriers
Butyrylcholine esterase BchE (NM_000055) adds BglII and BamHI restriction enzyme sites by PCR method to two ends, will
Butyrylcholine esterase endonuclease bamhi links to pRcCMV carriers by the method for molecular cloning, is built into BchE-pRcCMV)
According to 300ng, 100ng, 30ng, 10ng is measured per hole, is transiently transfected by way of liposome transfection into aim cell strain.
After culture 72 hours, the proliferative conditions that 50ul/ hole Cell Titer Glo detect cell, concrete outcome such as Fig. 2 are added into culture plate
It is shown.In Fig. 2, every four columns are corresponded in a kind of experimental result of cell line, each group column, from left to right four posts
Shape bar corresponds to the addition in 300ng, 100ng, 30ng, 10ng butyrylcholine esterase-pRcCMV carriers/hole respectively.
Embodiment 3
Acetylcholinesterase Tumor growth inhibition is tested：
Male Balb/c nude mices (surrounding is big, 16-20g) pass through subcutaneous vaccination 5*106Individual A549 cells, when gross tumor volume reaches
100mm3, take out tumour and be cut into uniform tissue block, tumor tissue is seeded to nude mice after new nude mice, inoculation random
It is grouped Saline (physiological saline), AchE Group (acetylcholinesterase treatment group), BchE Group (butyrylcholine esterases
Treatment group) every group 8；When gross tumor volume reaches 100mm3When, give AchE-pGS, BchE-pRcCMV by gavage mode
(Quaternary Ammonium Salt of Chitosan is dissolved in PBS to chitosan compound, is configured to 0.5% (w/v) solution, pH7.6；AchE and BchE plasmids
TE buffer solutions are dissolved in, 0.1mg/ml solution is configured to；By chitosan solution and plasmid solution according to volume ratio 1：1 prepares),
Daily 400ul, successive administration 4 weeks measures weekly body weight and tumor volume change, and specific experiment result is as shown in Figure 2.
In summary, the present invention effectively overcomes various shortcoming of the prior art and has high industrial utilization.
The above-described embodiments merely illustrate the principles and effects of the present invention, not for the limitation present invention.It is any to be familiar with this skill
The personage of art all can carry out modifications and changes under the spirit and scope without prejudice to the present invention to above-described embodiment.Therefore, such as
Those of ordinary skill in the art without departing from disclosed spirit with completed under technological thought all etc.
Modifications and changes are imitated, should be covered by the claim of the present invention.
Claims (10)
1. the purposes of acetylcholinesterase, butyrylcholine esterase or their mutant in preparing or screening the medicine for the treatment of tumour, institute
The medicine for the treatment of tumour is stated medicine is administered orally.
2. purposes as claimed in claim 1, it is characterised in that the purposes be specially acetylcholinesterase, butyrylcholine esterase or
Purposes of the recombinant expression carrier of their mutant in preparing or screening the medicine for the treatment of tumour.
3. purposes as claimed in claim 2, it is characterised in that the expression vector be selected from promoter, eucaryon replication orgin,
The non-integrating vectors of prokaryotic origin of replication.
4. purposes as claimed in claim 3, it is characterised in that the promoter is selected from CMV, PGK or EF-1, the eucaryon
Replication orgin is selected from SV40 or OriP, and the prokaryotic origin of replication derives from pUC or pBR322Ori.
5. purposes as claimed in claim 1, it is characterised in that the tumour is selected from non-small cell lung cancer, stomach cancer, liver cancer, mammary gland
Cancer, colorectal cancer, prostate cancer, glioma, head and neck cancer or blood tumor.
6. a kind of pharmaceutical composition, described pharmaceutical composition include the acetylcholinesterase of therapeutically effective amount, Acetylcholine esterase mutant,
The recombinant expression carrier and medicine of butyrylcholine esterase or butyrylcholine esterase mutant also include pharmaceutically acceptable carry
Body, described pharmaceutical composition is oral formulations.
7. pharmaceutical composition as claimed in claim 6, it is characterised in that the expression vector is selected to be replicated with promoter, eucaryon
The non-integrating vectors of starting point, prokaryotic origin of replication.
8. pharmaceutical composition as claimed in claim 7, it is characterised in that the promoter is selected from CMV, PGK or EF-1, institute
State eucaryon replication orgin and be selected from SV40 or OriP, the prokaryotic origin of replication derives from pUC or pBR322Ori.
9. pharmaceutical composition as claimed in claim 6, it is characterised in that the pharmaceutically acceptable carrier is chitosan solution.
10. pharmaceutical composition as claimed in claim 6, it is characterised in that described pharmaceutical composition is used to treat tumour.
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Cited By (1)
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| CN110343682A (en) * | 2018-04-03 | 2019-10-18 | 香港理工大学深圳研究院 | For detecting the mutant enzyme and preparation method of organophosphorus pesticide |
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| WO2005066337A2 (en) * | 2004-01-09 | 2005-07-21 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Compounds, pharmaceutical compositions and therapeutic methods of preventing and treating diseases and disorders associated with amyloid fibril formation |
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Application publication date: 20170811 |