WO1993022433A2 - Medicament permettant de traiter l'homme, les animaux et les plantes par therapie genetique, dans le but notamment de bloquer la proliferation de virus et les carcinogenes et procede de fabrication dudit medicament - Google Patents

Medicament permettant de traiter l'homme, les animaux et les plantes par therapie genetique, dans le but notamment de bloquer la proliferation de virus et les carcinogenes et procede de fabrication dudit medicament Download PDF

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WO1993022433A2
WO1993022433A2 PCT/DE1993/000374 DE9300374W WO9322433A2 WO 1993022433 A2 WO1993022433 A2 WO 1993022433A2 DE 9300374 W DE9300374 W DE 9300374W WO 9322433 A2 WO9322433 A2 WO 9322433A2
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dna
virus
medicament
rna
cells
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PCT/DE1993/000374
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German (de)
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WO1993022433A3 (fr
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Frank Andreas Harald Meyer
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Frank Andreas Harald Meyer
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Priority to EP93911729A priority Critical patent/EP0677103A1/fr
Publication of WO1993022433A2 publication Critical patent/WO1993022433A2/fr
Publication of WO1993022433A3 publication Critical patent/WO1993022433A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1241—Nucleotidyltransferases (2.7.7)
    • C12N9/1276—RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae

Definitions

  • the invention relates to a medicament for the gene therapy treatment of humans, animals and plants, in particular for blocking the multiplication of viruses and the tumor genes, and to a method for producing the medicament.
  • Retroviruses cause diseases in the human and animal body, among other things. Retroviruses occupy a special position. They are single or double-stranded RNA viruses that are replicated and expressed via a double-stranded DNA form. This form of DNA is synthesized by the virus enzyme reverse transcriptase. Many retroviaries carry oncogenes. The acquired weakness of the immune system - AIDS (Acquired Immune Deficiency Syndrome) - in which the patients die from a progressive weakening of the immune system is also linked to an infection by a retrovirus.
  • AIDS Abund Immune Deficiency Syndrome
  • the invention has for its object to provide a medicament, in particular for blocking the virus multiplication and for blocking the tumor genes, as well as a method for producing the medicament.
  • the therapy consists of a vaccination that the patient feels like other vaccinations.
  • virus envelopes themselves cause a body's own immune response by increasing the formation of antibodies against these non-reproducible envelopes, which also destroy the viruses, which are still formed to a small extent in unreached cells before further infections of other cells can occur.
  • the body's own defense reactions are therefore promoted.
  • the immune system can be supported, in particular with regard to points (d) and (e), in the fight against other viral infections. This advantage is particularly noticeable in the treatment of the immune deficiency disease AIDS, since secondary infections can be effectively combated.
  • the immune system of each organism previously contaminated by viruses can defend itself more specifically against other pathogenic substances, or the respective body can use its energies in another way, which on the one hand is beneficial for the organism, freed from some flagella should set a longer life expectancy and on the other hand better growth (higher life expectancy of humans and greater yields in agricultural products).
  • the drug is buffered against most mutations of the viruses to be controlled because slight differences in the opposite sequence do not have a noticeable effect, since the hybridization is not prevented due to the length of the opposite strands.
  • RNA ribonucleic acid
  • DNA deoxyribonucleic acid
  • mRNA messenger RNA or messenger RNA
  • the result is an opposite mRNA, the sequence of which is complementary to the normal mRNA transcripts. Is opposite mRNA transcribed in a sufficiently large quantity, it will be "with -the viral mRNA". "- hybridize and prevent the synthesis of proteins that are essential for the survival of the lytic and temperate cycle of retroviruses.
  • the introduced DNA sequence is transcribed into mRNA that hybridizes with the viral mRNA that codes for reverse transcriptase. So that's how
  • RNA double helix formed in the cell of the gene of the reverse transcriptase on the mRNA strand prevents the incorporation into protein shells because they only provide a limited space. It also prevents a specific arrangement of the viral genome that would be essential for virulence.
  • the processes described can be supported by incorporating further, opposite viral genes of such retroviruses into the host genome, which then also hybridize with the retrovirus genome and thus inhibit the synthesis of protein envelopes of the viruses or virus-specific proteins.
  • This highly specific enzyme made up of proteins therefore has an amino acid sequence and hence an mRNA sequence that is unique to reverse transcriptase. Hybridizations with host cell-specific mRNA strands are therefore hardly achievable. The same applies to other virus gene segments.
  • the gene for the opposite strand must be given a very strong promoter, ie a special DNA sequence, so that sufficient mRNA is formed.
  • the promoter contains both the starting point for RNA synthesis and the information on where to begin. The promoter also ensures that the concentration of the mRNA within the cell is high enough to ensure sufficient resistance to invading viruses.
  • the "cap” structure which consists of a 7-methylguanine residue and a triphosphate coupled to it, is attached to the 5 'end of the primary transcript that was first synthesized during transcription, but does not inhibit hybridization,
  • So episites unique base sequences in the modified antisense strand, have to be created, which are incorporated into homologous chromosites, provirus installation sites, of cellular introns.
  • the provirs of adenoviruses, miopapoaviruses and retroviruses are incorporated into non-homologous recombination, a process that requires little or no homology between the cellular and viral DNAs and no special recombination enzymes, in a wide variety of locations, including in exons of the host cell genome.
  • a controlled, site-specific integration is achieved in that the integration takes place by means of homologous recombination between nucleotide sequences in non-functional DNA sections of the host cell genome and the homologous sequences in the peripheral regions of the opposing genetic information.
  • the LTR long terminal repeat
  • the built-in provirus becomes more cellular from short duplications Flanked sequences whose length is virus-specific and whose sequence varies from installation site to installation site. Integrated proviruses of oncoviruses therefore have a transposon structure. For understandable reasons, such structures must be excluded for the modified opposing strands.
  • a further increase in the concentration of the opposing mRNA can be achieved by the frequency of the corresponding DNA sequence in the genome.
  • the body is first flooded with counter-rotating mRNA revertase or the corresponding counter-rotating genes, which through a special modification penetrate the plasma membrane of the cell. This will immediately interrupt the virus cycle. Further synthesis and further infection are prevented. The immune system can stabilize and fight the virus.
  • the opposing mRNA revertase is rewritten by the revertase itself into opposing DNA revertase. If the latter is present in sufficient quantity, the DNA revertase can be incorporated into the host genome of plant cells in such a way that it arrives with great certainty in front of the host's own promoters and then independently forms opposing RNA revertase. In other cases, repetitive sequences arise with the consequences described above. The same applies to other gene segments in the virus genome.
  • this DNA is preferably designed like a transposable element, which makes it easier for the DNA to integrate into the genome, move there and possibly multiply. It is relatively likely that this element, which should have a strong promoter, will be integrated into a group of active genes (operon model). The same effect is achieved if the DNA strand is embedded in LTR sequences, as is generally the case with viruses.
  • a second step is to introduce permeable reverse DNA revertase into the body, which can only be built into the genome of the cells when cells divide. This treatment has to be carried out over such a long period of time that all itotically dividing cells are reached. In this way, the germ cells are also artificially mutated, resulting in a ' Retrovirus immunization takes place in the offspring. The virus infection of the offspring can thus also be prevented. The required amount of DNA can be generated by gene cloning.
  • the binding of certain chemical compounds to the ends of the nucleic acid molecules is necessary, as in the case of the "cap” structure, which consists of a 7-methylguanosine residue and a triphosphate coupled to it, which is easily achieved by a any known enzyme can be hydrolyzed and broken down.
  • Special chemical groups or compounds can be used to strengthen the binding of the coding viral mRNA with the counter-rotating mRNA, which is used for acute treatment.
  • double-stranded retroviruses which have to be single-stranded at some point when they enter the cell, could also be switched off, because the opposite mRNA binds to the strand so tightly that they cannot be separated by thermal or enzymatic cleavage.
  • the complex persists until the mRNA of the virus disintegrates or is broken down, while the longer-lived counter-mRNA stabilized by certain complexes can enter into a new pairing and is an artificial biocatalyst.
  • a certain problem is the transduction of mRNA and DNA, which represent giant molecules as opposing genes, into the eukaryotic cell, whereby the plasma membranes form the barrier that has to be overcome.
  • a very good way of finding the infected cells in the organism and treating them selectively is to use gl cosylated liposomes or the virus protein envelopes themselves as carriers. It is not the intact virus genome that is introduced into the virus protein envelopes, but rather its own counter-rotating nucleic acids and possibly certain enzymes, which are then introduced into the affected cells in a highly selective manner as genetic material. Thus cells that no longer mitotically divide can also be treated, because the receptors of these cells are not only reached by the pathogenic viruses, but also by the medication.
  • the opposite complementary virus RNA is identical in length to the original virus RNA, there are no space problems in the associated viral protein shells, which ultimately dock onto the same receptors to which the normal virulent viruses respond, based on the entire rewritten genome.
  • the body's immune response to the virus envelopes can itself cause immunity. As indicated briefly above, the body reacts with its immune system to the virus protein shells in order to destroy them. The general difficulties that the body has with the constantly mutating viruses are known. In principle, this antigen-antibody response, especially before a virus infection, is only advantageous, even if large portions of the corresponding medication, ie large amounts of the anti-viruses, are destroyed in the process. The organism strengthens thereby his fight against the viruses damaging him.
  • Passive immunization is also conceivable in the form of a vaccination by taking blood from a healthy organism immunized with virus envelopes with a correspondingly stronger immune system in order to administer the antibodies as a vaccine.
  • Infected organisms also have antibodies in their blood that could be used if their immune systems are strong enough.
  • liposomes that contain the corresponding glycoproteins would also be able to supply the respective target cells with the opposite genetic information and the associated enzymes.
  • HIV-positive or, for example, leukemia patients whose leukemia was caused by viruses can be significantly supported with immune cells treated in vitro:
  • Corresponding cells can also be used outside of a living organism, i.e. in vitro, according to the same principle by anti-viruses the respective viral genome of opposing RNA or opposing DNA and the corresponding respective enzymes.
  • Acute people with AIDS immunodeficiency can thus use resistant immune defense cells that contain genetic information that is opposite to the virus genomes, such as T helper lymphocytes, macrophages, monocytes, antigen-presenting dendritic follicular reticular lines, Epstein-Barr virus-transformed B-lymphoblastoid cells or other cells with the appropriate receptors can be effectively supported in their immune defense by transfusing these new, grown resistant immune cells or by returning the now resistant, own cells treated outside the body.
  • the same approach is also suitable for supporting, for example, leukemia patients whose blood cancer was also caused by oncogenes.
  • the fertilized egg (zygote) is spiked with reverse DNA. This means that every body cell in the resulting organism - i.e. every nerve, muscle and immune cell - is immune to retroviruses. Resistance is achieved that makes any drug treatment against retroviruses superfluous. Immunity is also passed on to offspring.
  • the drug described is suitable for use with all prokaryotes and eukaryotes, that is, both with single and with Multicellular, i.e. humans, animals and plants. It is suitable for both prophylactic vaccination and acute treatment.
  • the self-assembly mechanism is used to integrate the specified antisense RNA or DNA strands and the corresponding enzymes into the appropriate, suitable virus envelopes, in order to transport these virus envelopes into the respective affected cells with the find corresponding receptors.
  • thermodynamic laws and / or kinetic determinations i.e. Reactions dependent on the reaction pathway are the property of complicated biological structures that are composed of macromolecular building blocks by themselves.
  • the ability to self-organize means that the information in the macromolecules is sufficient to determine the correct virus structure. It is precisely this ability that is inherent in all viruses when building their complete structure. Only the external medium, i.e. the corresponding pH value, favorable temperature conditions, the correct ion concentration and the addition of suitable enzymes, are decisive for the independent structure of the virus structure.
  • antisense RNA or DNA is to be accommodated in a suitable virus protein envelope
  • the original RNA or DNA is first removed in vitro, for example by changing the pH, so that the envelope breaks down into its protein components. Now you can remove the original RNA or DNA from the solution. Now add the appropriate antisense genes to these protein building blocks, which - as mentioned above - take up the same space as the original genetic information. Since most viruses have already integrated their own enzymes into their shells, one is therefore able to add these enzymes or other substances to this solution.
  • the pH value is brought back to its original state, then .
  • the self-assembly reaction described above occurs, in which the virus envelope is built up around the nucleic acids or around the enzymes.
  • viruses to be combated are cloned beforehand, it is possible to industrially produce any quantity of virus with antisense genes as a medicament.
  • the advantage of the method is that it is applicable to all types of viruses.
  • the production process must be adapted to each virus species with regard to the external medium and with regard to the structural properties.
  • the self-assembly function works, among other things, through the lipid envelope present in the capsid of some types of virus and / or due to essential template-like molecular arrangements within the host cells that were synthesized by the viruses themselves or that are present in these cells from the beginning. Mechanism outside of the corresponding host cells does not.
  • glycoproteins in liposomes that must be able to do the respective to carry opposing genetic material so fix that these liposomes can deliver their contents to the respective host cells in a targeted manner, just like the viruses, by specifically docking to the receptors of the corresponding host cells.
  • the building blocks of the anti-viruses are now able to use the template-like ones Assemble structures.
  • the anti-viruses are taken from the budding or lysing these cells in culture in order to deliver them to the organisms suffering from the pathogenic viruses.
  • HIV-I and HIV-II have almost the same properties, but very different ribonucleic acids due to their very little relationship «.
  • the corresponding gag and pol genes of HIV-I and HIV-II are only 60% related, the relationship of the respective env genes is 40%. If one modifies the opposite ribonucleic acids in such a way that these opposite strands do not undergo any noteworthy hybridizations with the respective other type of virus and thereby ensures that the otherwise necessary complementarity to the original strand is maintained, one could use a cell culture infected with HIV-I move RNA opposing to HIV-II.
  • the protein envelopes of HIV-II can be treated in the same way with genes opposite to HIV-I.
  • the viruses budding from the host cells can now either contain their own real genetic information or the opposite of the other species.
  • H (12.3 a) are, for example, very light, non-mutagenic emitters, which, however, have a relatively long half-life compared to the harder emitter 32 P. In return, 32 P only has a half-life of 14 days.
  • 32 P With the help of the principle of a cell sorter, one could now differentiate and separate the anti-viruses from the pathogenic viruses that have no radioactive labeling. The HIV virus yield is then only 25% because the two strands of nucleic acid must be in opposite directions. Both strands within an anti-HI virus must have a radioactive label.
  • nucleic acids which are complementary to the respective other virus types are linked to fluorescent molecules before they are injected into the cells of the cell cultures, so that the anti-viruses synthesized in these cells are separated from one another by a cell sorter by the other normally pathogenic viruses also built up there can be distinguished and separated.
  • both HIV viruses have the glycoproteins 120 integrated in their capsids, they dock onto the same CD-4 receptors, so that the same target cells can be supplied with the drug when these HI anti-viruses are injected into the respective patient . Infestation of the same host cells is one of the reasons for the same symptoms that they produce in their hosts, despite their relatively low relatives.
  • Another starting point is the corresponding disease-causing virus, against which resistance is to be made possible by the production of a gene therapy medicament.
  • the virus envelope is broken down by changing the pH and / or the temperature and / or the ion concentration and / or by adding enzymes.
  • RNA-DNA hybrid arises that DNA polymerase is added after washing. The latter replaces RNA with DNA.
  • a DNA double helix is created which corresponds to the provirus genome of the retrovirus. This is still capable of producing normal viral RNA. If DNA viruses are used, steps (5) and (6) can be omitted.
  • virus genome is cut so that virus-specific promoters can be cut out and artificial promoters can be integrated, which ensure the transcription on the next strand and thus the production of the opposite RNA.
  • virus-specific promoters can be cut out and artificial promoters can be integrated, which ensure the transcription on the next strand and thus the production of the opposite RNA.
  • intron homology, splice sequences, start and stop codons is followed.
  • Liga ⁇ e an enzyme that firmly binds newly combined DNA fragments, is added, whereby the DNA fragments assembled at the sticky ends are joined to form a stable double helix.
  • the strands are then allowed to hybridize with two excess chemically synthesized DNA oligo-nucleotides, each 15 to 20 nucleotides long and in sequence to two sections that are separated by any number of nucleotides.
  • the two oligo nucleotides serve as specific primers for in vitro nthe ⁇ e Sy 'of the DNA, which is catalyzed by the DNA polymerase.
  • this enzyme copies the DNA between the sequences that correspond to the oligonucleotides.
  • a virus whose protein envelope is suitable as a means of transport for the corresponding counter-rotating DNA, is changed by changing the pH and / or ion concentration and / or temperature and / or by adding suitable chemical substances into the elementary building blocks of the virus envelope and into it viral genome decomposed.
  • the purified viral envelope elemental proteins are incubated with the opposite RNA or DNA strand.
  • template-like molecules are normally built up by viruses within their host cells, it is necessary to crosslink a cell with genes which, with the help of a promoter, also synthesize these structures without providing the pathogenic viruses and clone this cell so that it can be cloned the individual anti-virus building blocks in these cell cultures according to the natural mechanisms can store together.
  • genes for example they could encode the required lipid envelope of the retroviruses, should be incorporated into the intron sequences of the genome.
  • the virus envelopes are assembled in a suitable environment, depending on the virus type, outside or within suitable host cells kept in cell culture, around the opposite RNA or DNA strand (self-assembly).
  • the anti-viruses can then be separated from the normal viruses by a fluorescent label or by radioactive labels using a cell sorter and separated.
  • RNA polymerase (1) Starting from process step (10), the opposite DNA is mixed with RNA polymerase and other components important for transcription, such as triphosphate nucleotides.
  • the RNA polymerase continuously produces new counter-rotating single strand RNA in large quantities.
  • RNA polymerase II and the other components necessary for RNA synthesis are added to the opposite gene. Mass production of reverse RNA occurs.
  • mRNA is extracted from host cells and introduced into the process.
  • the vaccination should take place on several dates, each with anti-viruses grown in different cell cultures. So that not too many corresponding receptors of the target cells are occupied at the same time, several vaccination steps with appropriate anti-virus doses and longer-lasting infusions are sensible for even distribution in the body.
  • CD-4 receptors for example in the case of HIV infection
  • Anti-viruses that escape from their host cell during the disengagement process like the original viruses, camouflaging with host cell membrane fragments, produce, on the basis of the fact that, in cell cultures whose cells come from a foreign organism, antibodies in the patient which would lead to strong defense reactions if vaccinated again with anti-viruses of the same cell culture.
  • the drugs can be optimized against most pathogenic virus types after a relatively short trial, based on the knowledge already available, in such a way that even shortly after the vaccination, any signs of vaccination, such as fever attacks by the patient, are either completely avoided or at least can be reduced sharply.
  • Such an exchange of the protein shells of a virulent virus with a harder shell of another virus type would, however, have the major disadvantage that the antibody response of the host's immune system against these pathogenic viruses to be combated would not be further strengthened for more effective control.

Abstract

Dans l'organisme de l'homme et dans celui des animaux, les maladies sont induites entre autres, par des virus. De nombreux rétrovirus sont porteurs d'oncogènes. Pour lutter contre les rétrovirus, on essayait jusqu'à maintenant d'intervenir sur des rétrovirus accomplis. Les inconvénients de la thérapie connue résident dans le fait que l'on ne peut empêcher l'apparition de diverses formes d'effets secondaires qui sont lourds à gérer pour le patient traité et que s'il est avéré que l'on peut retarder l'évolution de nombreuses maladies, on n'arrive pas pour autant à les enrayer. Ce nouveau médicament est adapté notamment pour bloquer la prolifération de virus et pour bloquer les carcinogènes. Ce médicament contient des enveloppes de virus qui s'arriment aux récepteurs des cellules souches connues. Ce médicament comprend des cellules prélevées sur l'organisme, qui ont été traités avec des antivirus. Ce médicament comprend des cellules prélevées sur l'organisme et traitées avec les liposomes glucolysés appropriés. L'utilisation de ce médicament ne génère qu'un très petit nombre d'effets secondaires pénibles pour le patient traité et permet de guérir des maladies.
PCT/DE1993/000374 1992-04-28 1993-04-28 Medicament permettant de traiter l'homme, les animaux et les plantes par therapie genetique, dans le but notamment de bloquer la proliferation de virus et les carcinogenes et procede de fabrication dudit medicament WO1993022433A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP93911729A EP0677103A1 (fr) 1992-04-28 1993-04-28 Medicament permettant de traiter l'homme, les animaux et les plantes par therapie genetique, dans le but notamment de bloquer la proliferation de virus et les carcinogenes et procede de fabrication dudit medicament

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EP9200923 1992-04-28
ATPCT/EP92/00923 1992-04-28
DEP4238879.1 1992-11-19
DE4238879 1992-11-19

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EP0650370A1 (fr) * 1992-06-08 1995-05-03 The Regents Of The University Of California Procedes et compositions permettant de cibler des tissus specifiques
DE19503082A1 (de) * 1995-02-01 1996-08-08 Univ Ludwigs Albert Gegenstand und Verfahren zur bevorzugt transienten Expression und möglichen Translation spezifischer RNA im cytoplasmatischen Bereich höherer eukaryontischer Zellen

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0650370A1 (fr) * 1992-06-08 1995-05-03 The Regents Of The University Of California Procedes et compositions permettant de cibler des tissus specifiques
EP0650370A4 (fr) * 1992-06-08 1995-11-22 Univ California Procedes et compositions permettant de cibler des tissus specifiques.
DE19503082A1 (de) * 1995-02-01 1996-08-08 Univ Ludwigs Albert Gegenstand und Verfahren zur bevorzugt transienten Expression und möglichen Translation spezifischer RNA im cytoplasmatischen Bereich höherer eukaryontischer Zellen

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