KR20130103955A - Pseudotype replication-competent retrovirus two-vector system for treatment of abnormally proliferating cells - Google Patents

Abstract

PURPOSE: A vector system is provided to be used as a composition for abnormally proliferating cell-targeting gene delivery and a composition for preventing or treating diseases causing the abnormally proliferating cells by transfection of a cell line. CONSTITUTION: A pseudotyped replicable retrovirus vector system for treating abnormally proliferating cells is prepared by inserting an abnormally proliferating cell therapeutic gene. The vector system comprises: a first recombinant expression vector containing murine leukemia virus (MuLV)-Gag gene and MuLV-Pol gene; and a second recombinant expression vector containing gibbon ape leukemia virus (GaLV) gene. The abnormally proliferating therapeutic gene is inserted into the first and second recombinant expression vectors. The second recombinant expression vector contains a vector.

Description

Pseudotype Replication-Competent Retrovirus two-vector system for treatment of abnormally proliferating cells}

The present invention relates to a pseudotype replicable retroviral vector system and its use which enables efficient gene delivery to abnormally dividing aberrant proliferation cells.

Proliferation is caused by cell development through the cell cycle which divides one cell into two cells. The cell cycle consists of five stages, G ₀ , G ₁ , S, G ₂ , and M phases. During the G ₀ group, the cell is stopped, most of the cell body is in this step. During stage G ₁ , the cells respond to signals to divide to produce RNA and proteins necessary for DNA synthesis, and cells during stage S (SE early in S stage; SM in mid S stage; and SL in late stage S). Duplicates its DNA, during G ₂ phase, the cell synthesis continues to grow and prepare for mitosis, and during mitosis (M), the cell divides into two daughter cells. Aberrant proliferation may be caused by such alterations in cell cycle progression, which may result from overexpression of genes, mutation of regulatory genes, or defects in DNA damage checkpoints (Hochhauser D., Anti-Cancer Chemotherapeutic Agents, 8: 903, 1997).

There are several types of aberrant cell disease. Representative aberrant cell diseases include cancer, bacterial infections, immune rejection of organ transplantation, solid tumors, viral infections, autoimmune diseases (eg arthritis, lupus, inflammatory bowel disease, Sjogren's syndrome, multiple sclerosis), or combinations thereof. Can happen by

The present invention provides a pseudotype replicable retroviral vector system into which aberrant proliferation genes are inserted. The vector system comprises a first recombinant expression vector comprising a MuLV (Murine Leukemia virus, MuLV) -Gag gene and a MuLV-Pol gene. It comprises a second recombinant expression vector containing GaLV (Gibbon Ape Leukemia Virus) -Env gene, the apoptotic cell treatment gene is inserted into the first recombinant expression vector or the second recombinant expression vector, aberrant proliferation cell treatment To provide a pseudotype replicable retroviral vector system.

The present invention provides a retrovirus produced by transfecting a cell line with a vector system.

The present invention is to provide a composition for aberrant cell growth target gene delivery comprising a retrovirus.

In addition, the present invention is to provide a composition for preventing or treating aberrant cell-causing disease comprising the retrovirus.

The present invention provides a pseudotype replicable retroviral vector system into which aberrant proliferation genes are inserted. The vector system comprises a first recombinant expression vector comprising a MuLV (Murine Leukemia virus, MuLV) -Gag gene and a MuLV-Pol gene. It comprises a second recombinant expression vector containing GaLV (Gibbon Ape Leukemia Virus) -Env gene, the apoptotic cell treatment gene is inserted into the first recombinant expression vector or the second recombinant expression vector, aberrant proliferation cell treatment Pseudotype-replicable retrovirus vector systems are provided.

The first recombinant expression vector may include a vector of the cleavage map of FIG. 1.

The second recombinant expression vector may include a vector of the cleavage map of FIG. 2.

By inserting the aberrant cell therapy gene into the second recombinant expression vector, it may include a vector of the cleavage map of FIG.

The apoptotic cells may be noncancerous apoptotic cells derived from inflammatory diseases or aberrant proliferative vascular diseases.

Non-cancerous dysplasia cells derived from the inflammatory disease are inflammation-induced bone disease, degenerative arthritis, diabetes mellitus, autoimmune myositis, arteriosclerosis, stroke, liver cirrhosis, meningitis, inflammatory gastric ulcer, gallbladder stones, kidney stones, sinusitis, rhinitis, conjunctivitis , Asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular disease, glomerulonephritis, inflammatory skin disease, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Behcet's disease ), Ulcerative colitis, Crohn disease, psoriasis, atopic dermatitis, contact dermatitis, eczema dermatitis, seborrheic dermatitis, lichen planus, chronic simple Lichen simplex chronicus, pemphigus, bullocks, epidermolysis bullosa, urticaria, angioedema oedema), vasculitis, erythema, cutaneous eosinophilia, nummular dermatitis, systemic deprivation dermatitis, stagnation dermatitis, diseases of the sebaceous glands, percutaneous dermatitis, beard pseudofolliculitis, drug rash, polymorphism It may be aberrant proliferation cells derived from erythema multiforme, erythema nodosum, granuloma annulare or pelvic inflammatory disease (PID).

Non-cancerous dysplasia cells derived from the dysplastic vascular disease include atherosclerosis, atherosclerosis, restenosis and stenosis, vascular malformations, vascular narrowing associated with hemodialysis, post-transplant arteriopathy, vasculitis, vascular disease Inflammatory disease, Digejji syndrome, hereditary hemorrhagic capillary dilator (HHT), keloid scar, bullous disease, hyperproliferative vitreous syndrome, prematurity retinopathy, choroidal neovascularization, macular degeneration, diabetic retinopathy, primary neovascular hyperplasia, primary pulmonary hypertension , Asthma, nasal polyps, inflammatory bowel and periodontal disease, endometriosis, ovarian cysts, ovarian hyperstimulation syndrome, arthritis, rheumatoid arthritis, chronic arthritis, synovial inflammation, osteoarthritis, osteomyelitis, osteoproliferation, pneumonia or vascular leakage Aberrant proliferation cells derived from the syndrome.

The present invention provides a retrovirus produced by transfecting a cell line with the vector system.

The present invention provides a composition for aberrant cell growth target gene delivery comprising the retrovirus.

The present invention provides a composition for preventing or treating aberrant cell-causing disease, including the retrovirus.

In the present invention, the therapeutic gene can be added to both the first recombinant expression vector including the MuLV-Gag gene and the MuLV-Pol gene, which is the aberrant cell targeting vector, and the second recombinant expression vector including GaLV-Env. Therefore, various therapeutic foreign genes can be inserted without any restriction on the size of the insert gene, and the vector can transmit foreign genes infected with abnormal proliferation cells with abnormal cell division with a high infection rate. It can be used as a pharmaceutical composition for preventing or treating abnormal proliferation-causing diseases by confirming that it is safe because it can transmit foreign genes only to the area of abnormal-proliferating cells without affecting the cells. will be.

1 shows a cleavage map of a first recombinant expression vector including a Gag gene and a Pol gene.
Figure 2 shows a cleavage map of the second recombinant expression vector containing the GaLV-Env gene.
Figure 3 shows that the therapeutic gene is added to the second recombinant expression vector.
4 and 5 relate to subcloning of sRCRgp-RFP,
FIG. 4 shows that pRCR (FvGEL199) was digested with Sca I, Pme I, treated with T4 DNA polymerase and then self-bound to remove the FvGEL199Env sequence.
FIG. 5 shows the insertion of the mCMV promoter-RFP fragment digested with sRCRgp plasmid with EcoR I and PCR-amplified from pLentiM1.4-monomerRFP to insert marker genes (RFP).
FIG. 6 relates to subcloning of spRCRe (GaLV-Env) GFP. FIG. 6A shows that pMFG-eGFP-Puro was digested with Xho I and Cla I and then pLenti by PCR in order to insert the mCMV promoter and GFP sequence. It will then combining them with that mCMV promoter fragment amplified from -eGFP -M1.4-eGFP, 6B is next pMYK-ef1-GaLV-Env in amplifies the GaLV-Env sequence Pme of pMFG-mCMV-GFP2 (Figure 3A) It is inserted into the area decomposed into I.
Figure 7 shows the structure of a semi-replicable retroviral vector expressing a fluorescent marker protein, Figure 8A shows that sRCRgp-RFP contains not only LTR but also Gag-Pol expression structure and RFP sequence in sRCRe ( MuLV-Env) -GFP contains not only expression markers but also MuLV-Env expression structures and GFP sequences, and FIG. 8B shows the exchange of the MuLV-Env gene in sRCRe (MuLV-Env) -GFP with a GaLV-Env gene.

The present invention is a pseudotype replicable retroviral vector system into which aberrant progenitor cell therapy genes are inserted, a retrovirus produced by transfecting a cell line with the vector system, and a composition for aberrant proliferation cell target gene delivery comprising the retrovirus. And it provides a composition for preventing or treating aberrant cell-causing disease.

Hereinafter, the present invention will be described in detail.

The present invention provides a pseudotype replicable retroviral vector system into which aberrant proliferation genes are inserted. The vector system comprises a first recombinant expression vector comprising a MuLV (Murine Leukemia virus, MuLV) -Gag gene and a MuLV-Pol gene. It comprises a second recombinant expression vector containing GaLV (Gibbon Ape Leukemia Virus) -Env gene, the apoptotic cell treatment gene is inserted into the first recombinant expression vector or the second recombinant expression vector, aberrant proliferation cell treatment Pseudotype-replicable retrovirus vector systems are provided.

The first recombinant expression vector includes a MuLV-Gag gene and a MuLV-Pol gene, and is not particularly limited in kind, and may preferably include a vector of the cleavage map of FIG. 1.

The second recombinant expression vector contains a GaLV-Env gene, which is not particularly limited in kind, and may preferably include a vector of the cleavage map of FIG. 2.

Since the Replication Competent Retrovirus (RCR) vector of the present invention is a nonlytic virus, it does not cause cell damage by the host immune system and does not produce antibodies to the virus. Is not very good as a gene carrier.

The Replication Competent is capable of producing a virus in the resulting infected or transformed cells when transfecting or transfecting the viral genes into animal cells highly infectious for a particular virus. It can mean having.

Since the replicable retrovirus enters the crack that breaks the nuclear membrane into another nucleus, it can only infect dividing cells, which can specifically infect abnormally dividing abnormal proliferation cells. Therefore, by preventing the transgene from being expressed in other normal cells, not only does it provide the safety of gene transfer to aberrant proliferation cells, but also increases the gene transfer efficiency because the virus can replicate.

The Gag gene may be a polyprotein constituting four proteins of the core of the retrovirus, the Pol gene represents a reverse transcriptase, and the Env gene may represent an envelope glycoprotein.

In the present invention, by transforming the Env gene of the retrovirus into the GaLV-Env gene can increase the virus propagation and genome delivery efficiency.

For example, as a second recombinant expression vector, a vector containing a mulv (Murine Leukemia virus) envelope protein (sRCR) and a vector containing a GaLV envelope glycoprotein of the present invention (spRCR) were produced and compared, resulting in a GaLV-Env gene. When using an expression vector containing a higher viral infection rate and genome delivery efficiency can be.

In addition, the vector may include 5'-LTR and 3'-LTR, the smallest functional unit of the retroviral vector, and may insert the nucleotide sequence of the gene of interest to be carried between the LTRs.

The expression vector of the present invention is designed to deliver a foreign gene to abnormally dividing aberrant proliferation cells, the foreign gene can be inserted into the first recombinant expression vector or the second recombinant expression vector.

Conventional expression vectors were originally limited to the size of the foreign genes that can be inserted into the viral genome, whereas the vector system of the present invention divides the foreign insertion genes because one viral vector is divided into two. Because it can be placed in both vectors, not only can various genes be inserted in size but also replication and propagation can proceed as well as using one viral vector.

The foreign gene is not particularly limited, but may preferably be an aberrant cell therapy gene.

The apoptotic cells may mean that cell division occurs at an inappropriately high level due to the proliferation of cells deviating from the usual, suitable, or predicted course. In one example, aberrant proliferation cells may include inadequate proliferation of cells that have damaged or deleted DNA or other cellular components.

The apoptotic cells are not particularly limited in their kind, and may include noncancerous apoptotic cells derived from inflammatory diseases or aberrant proliferative vascular diseases.

The noncancerous apoptotic cells derived from the inflammatory disease are not particularly limited in their kind, and include inflammation-induced bone disease, degenerative arthritis, diabetes mellitus, autoimmune myositis, arteriosclerosis, stroke, liver cirrhosis, meningitis, inflammatory gastric ulcers, and gallbladder stones. , Kidney stones, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular disease, glomerulonephritis, inflammatory skin disease, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis ( Ankylosing spondylitis, Behcet's disease, ulcerative colitis, Crohn disease, psoriasis, atopic dermatitis, contact dermatitis, eczema dermatitis, seborrheic dermatitis, Lichen planus, lichen simplex chronicus, pemphigus, bullus pemphigus, epidermal bleb (Epid) ermolysis Bullosa, urticaria, angioedema, vasculitis, erythema, cutaneous eosinophilia, nummular dermatitis, systemic deprivation dermatitis, stagnation dermatitis, diseases of the sebaceous glands, Oral dermatitis, whisker pseudofolliculitis, drug rash, erythema multiforme, erythema nodosum, granuloma annulare or pelvic inflammatory disease (PID: Pelvic Inflammatory Disease) It may include.

Noncancerous apoptotic cells derived from the aberrant proliferative vascular disease are not particularly limited in its kind, and include atherosclerosis, atherosclerosis, restenosis and stenosis, vascular malformation, vascular stenosis associated with hemodialysis, and post-graft arterial disease. (transplant arteriopathy), vasculitis, vasculitis, Digejo syndrome, hereditary hemorrhagic capillary dilated disease (HHT), keloid scars, bullous disease, hyperproliferative vitreous syndrome, prematurity retinopathy, choroidal neovascularization, macular degeneration, diabetic retinopathy , Intraocular neovascularization, primary pulmonary hypertension, asthma, nasal polyps, inflammatory bowel and periodontal disease, endometriosis, ovarian cysts, ovarian hyperstimulation syndrome, arthritis, rheumatoid arthritis, chronic arthritis, synovial arthritis, osteoarthritis, Aberrant proliferation cells derived from osteomyelitis, osteoproliferation, pulmonary disease or vascular leakage syndrome, and the like.

The foreign gene is intended to be delivered to abnormally proliferating abnormal proliferation cells according to the purpose, and is not particularly limited in its kind, and may include hormones, enzymes, receptors, reporter genes, abnormal proliferation cell therapeutic genes, and the like.

For example, when the apoptotic cell treatment gene is inserted into the vector, it may be represented as a vector of the cleavage map of FIG. 3, and the apoptotic cell therapeutic gene may be inserted into the second recombinant expression vector.

In the present invention, it is possible to provide a retrovirus produced by transfecting a cell line with the vector system.

The kind of the cell line is not particularly limited, but examples thereof include human 293 cells, Hela cells, kenain D17 cells, and PEL4 PG4 cells.

The transfection method may be in accordance with methods known in the art, lipofectamine method (Invitrogen), micro-injection method (Capecchi, MR, Cell, 22: 479 (1980)), calcium phosphate precipitation method (Graham, FL et al., Virology, 52: 456 (1973)), electroporation (Neumann, E. et al., EMBO J., 1: 841 (1982)), liposome-mediated transfection (Wong, TK et al., Gene, 10:87 (1980)), DEAE-dextran treatment (Gopal, Mol. Cell Biol., 5: 1188-1190 (1985)) and gene bombardment (Yang et al., Proc. Natl Acad.Sci., 87: 9568-9572 (1990)).

The transfected cells are then cultured in a suitable medium. As a medium that can be used in the present invention, a medium conventionally used for culturing animal cells may be used. For example, Eagles' MEM (Eagle's minimum essential medium, Eagle, H. Science 130: 432 (1959)), a- MEM (Stanner, CP et al., Nat. New Biol. 230: 52 (1971)), Iscove's MEM (Iscove, N. et al., J. Exp. Med. 147: 923 (1978)), 199 medium ( Morgan et al., Proc. Soc.Exp. Bio.Med., 73: 1 (1950)), CMRL 1066, RPMI 1640 (Moore et al., J. Amer. Med. Assoc. 199: 519 (1967)) , F12 (Ham, Proc. Natl. Acad. Sci. USA 53: 288 (1965)), F10 (Ham, RG Exp. Cell Res. 29: 515 (1963)), DMEM (Dulbecco's modification of Eagle's medium, Dulbecco, R. et al., Virology 8: 396 (1959)), mixtures of DMEM and F12 (Barnes, D. et al., Anal. Biochem. 102: 255 (1980)), Way-mouth's MB752 / 1 (Waymouth, CJ Natl. Cancer Inst. 22: 1003 (1959)), McCoy's 5A (McCoy, TA, et al., Proc. Soc.Exp. Biol. Med. 100: 115 (1959)) and the MCDB series (Ham, RG et al., In Vitro 14:11 (1978)) There. For a description of the medium, see R. Ian Freshney, Culture of Animal Cells, A Manual of Basic Technique, Alan R. Liss, Inc., New York.

Retroviruses produced can be obtained by transfecting a cell line from the culture formed by the culture into the vector system.

The present invention provides a composition for aberrant cell growth target gene delivery comprising the retrovirus.

The cells targeted by the retrovirus may include all abnormally proliferating cells which are abnormally divided, and are not particularly limited in kind.

Such abnormally dividing aberrant proliferation cells cause various diseases in the human body, which may include inflammatory diseases, aberrant proliferative vascular diseases, and the like.

The apoptotic cells may be non-cancer cells derived from inflammatory diseases or aberrant proliferative vascular diseases.

The aberrant proliferative cells may refer to the above specification, and, for example, aberrant proliferative synovial cells of rheumatoid arthritis patients, aberrant proliferative vascular endothelial cells which cause atherosclerosis, aberrant proliferation red blood cells, granulocytes, which cause chronic myeloproliferative diseases, Platelets, apoptotic lymphocytes known as angiofollicular lymphoid hyperplasia, and cells of hyperplasia that cause various diseases.

The gene to be inserted into the retroviral vector may be selected according to the purpose of experiment, and is not particularly limited in its kind, and may include a gene expressing a hormone, an enzyme, a receptor, or a drug for treating apoptotic cell. Can be.

The composition of the present invention has a number of advantages as a carrier for delivering foreign genes to abnormally dividing aberrant proliferation cells. Since the retrovirus is a nonlytic virus, cell damage is not caused by the host immune system, and since the antibody against the virus is not generated, virus clearance does not occur and thus is excellent as a gene carrier. Because it can only infect cells, it specifically infects dividing apoptotic cells to prevent the expression of therapeutic genes in other normal cells, thereby providing more safety for cell therapists, and also because genes can be replicated. You can increase it.

The present invention provides a composition for preventing or treating aberrant progenitor cell-induced disease, including a retrovirus produced by transfecting a cell line with the vector system.

 The apoptotic cells may mean that cell division occurs at an inappropriately high level due to the proliferation of cells deviating from the usual, suitable, or predicted course. In one example, aberrant proliferation cells may include inadequate proliferation of cells that have damaged or deleted DNA or other cellular components.

The aberrant cell-causing disease may include cell proliferation of features associated with diseases, disorders caused, mediated, or caused by cell division at inappropriately high levels.

When preparing a pharmaceutical composition for preventing or treating apoptotic cell-induced disease comprising a retrovirus produced by transfecting a cell line with the vector system of the present invention, the retrovirus is 0.01 to 99% by weight relative to the total weight of the composition. It may be included as, but the scope of the present invention is not limited thereto.

The prophylactic or therapeutic compositions of the present invention are described in Remington's Pharmaceutical Science, latest edition; Mack Publishing Company, Easton PA], wherein the pharmaceutically acceptable carriers included are lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, know Nate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oils However, the present invention is not limited thereto.

In addition, the composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like in addition to the above components.

The pharmaceutical composition may be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrabronchial inhalation, intrauterine dural or intracerebroventricular, or the like.

Suitable dosages of the compositions of the present invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, patient's age, food, time of administration, route of administration, rate of excretion and response to reaction, and usually The skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis.

Compositions of the present invention may be prepared in unit dosage form by formulating with a pharmaceutically acceptable carrier and / or excipient, in accordance with methods readily available to those of ordinary skill in the art. It can be prepared by incorporation into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples illustrate the invention and are not intended to limit the scope of the invention.

< Example >

Example 1: Cell Culture

293T (human embryonic kidney) cells and U-87 MG (human glioma) cells were cultured in Dulbecco's Mini Essential Medium (DMEM, Thermo Hyclone) with 10% fetal bovine serum (Invitrogen) and antibiotics (Invitrogen). In all experiments, the cells were cultured in a 5% CO ₂ incubator in a cell culture vessel (100mm dish, 6well plate) and subcultured at 1: 5 when the cell frequency was 70-80%.

Example  2: creation of vectors

To create the sRCRgp-RFP vector containing the marker gene, RFP (see Figures 4 and 5), the FvGel199Env of pRCR (FvGEL199Env) was cut into Sca I and Pme I, and the part from the mCMV promoter to RFP of the pLenti M1.4-momomerRFP vector. Was cut into PpuM I and Not I for blunt end ligation.

To create the spRCRe (GaLV-Env) -GFP vector containing the marker gene, GFP (see Figure 6), the Xho I site after the gag of the MFG-eGFP-Puro vector and the Cla I site before 3'LTR were cut and pLenti. PCR was carried out from mCMV to eGFP of M1.4-eGFP by PCR. (Forward: Sal I- Pme I-mCMV, Reverse: Cla I-GFP) GaLV- between Gag and mCMV of MFG-mCMV-GFP2 vector produced. In order to insert the Env sequence, MYK-ef1-GaLV-Env was used as a template, and both primers were PCR using primers containing the Pme I position, and the previously made vector was cut into Pme I to bind with the Insert. ).

To insert the desired therapeutic gene instead of the marker gene, eGFP was cut into BamH I and Cla I and a multi cloning site was added to create a spRCR (GaLV-Env) -MCS vector.

To insert the TK gene (see Fig. 7) into spRCR (GaLV-Env) -MCS, pSXLC-TK vector was cut into Nco I and Xho I to make blunt ends with T4 DNA polymerase (TAKARA) and spRCR (GaLV-Env). -The MCS was cut into Pme I and combined with the insert after CIAP treatment.

In order to create the sRCRe (MuLV-Env) vector, the front of mCMV of MFG-mCMV-GFP2 was cut with Pme I. To make an Amphotropic MuLV-Env insert, the MuLV-Env portion of EQPAM-Am was PCR-ligated with primers containing the Pml I position in both the forward and reverse positions.

To insert the TK gene in sRCR (MuLV-Env) -RFP, cut both sides of the RFP with Hpa I, cut TK with Hpa I, Cla I in spRCR (GaLV-Env) -TK , and make it blunt. ligation).

Claims (10)

Pseudotype replicable retroviral vector system incorporating aberrant cell therapy gene,
The vector system includes a first recombinant expression vector comprising a MuLV (Murine Leukemia virus, MuLV) -Gag gene and a MuLV-Pol gene, and a second recombinant expression vector comprising a GaLV (Gibbon Ape Leukemia Virus) -Env gene. ,
Comprising the insertion of the apoptotic cell therapy gene in the first recombinant expression vector or the second recombinant expression vector, pseudotype replicable retroviral vector system for treating aberrant cell proliferation. The pseudotype replicable retroviral vector system according to claim 1, wherein the first recombinant expression vector comprises a vector of a cleavage map of FIG. 1. The pseudotype replicable retroviral vector system for treating aberrant proliferation cells according to claim 1, wherein the second recombinant expression vector comprises a vector of a cleavage map of FIG. The pseudotype replicable retroviral vector system for aberrant proliferation cell treatment according to claim 1, wherein the aberrant proliferation gene is inserted into a second recombinant expression vector and comprises a vector of a cleavage map of FIG. 3. The pseudotype replicable retroviral vector system according to claim 1, wherein the apoptotic cells are noncancerous apoptotic cells derived from an inflammatory disease or aberrant vascular disease. The method of claim 5, wherein the noncancerous apoptotic cells derived from the inflammatory disease are inflammation-induced bone disease, degenerative arthritis, diabetes mellitus, autoimmune myositis, arteriosclerosis, stroke, liver cirrhosis, meningitis, inflammatory gastric ulcer, gallbladder stones, kidney stones , Sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular disease, glomerulonephritis, inflammatory skin disease, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis , Behcet's disease, ulcerative colitis, Crohn disease, psoriasis, atopic dermatitis, contact dermatitis, eczema dermatitis, seborrheic dermatitis, flat lichen lichen planus, lichen simplex chronicus, pemphigus, bullus pemphigus, epidermolysis bullosa, urticari a), angioedema, vasculitis, erythema, cutaneous eosinophilia, nummular dermatitis, systemic deprivation dermatitis, stagnant dermatitis, diseases of the sebaceous glands, perioral dermatitis, beard pseudo Pseudomonas prophylaxis, drug rash, erythema multiforme, erythema nodosum, granuloma annulare or pelvic inflammatory disease (PID) Type Replicable Retrovirus Vector System. The method of claim 5, wherein the noncancerous apoptotic cells derived from the dysplastic vascular disease are atherosclerosis, atherosclerosis, restenosis and stenosis, angioplasty, vascular pathway narrowing associated with hemodialysis, and post-transplant arteriopathy Vasculitis, hereditary hemorrhagic capillary dilator (HHT), keloid scar, bullous disease, hyperproliferative vitreous syndrome, prematurity retinopathy, choroidal neovascularization, macular degeneration, diabetic retinopathy, intraocular neovascularization Vascular proliferation, primary pulmonary hypertension, asthma, nasal polyps, inflammatory bowel and periodontal disease, endometriosis, ovarian cysts, ovarian hyperstimulation syndrome, arthritis, rheumatoid arthritis, chronic arthritis, synovialitis, osteoarthritis, osteomyelitis, bone Pseudotype replicable retrobar for treating aberrant proliferation cells, aberrant proliferation cells derived from proliferative, pulmonary or vascular leakage syndrome Russ vector system. A retrovirus produced by transfecting a cell line with the vector system of any one of claims 1 to 7. Composition for aberrant cell proliferation gene delivery comprising the retrovirus of claim 8. Composition for preventing or treating aberrant cell-causing disease comprising the retrovirus of claim 8.

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