Biocompatible implant for the expression and in vivo secretion of a therapeutic substance

Abstract

The invention relates to an implant obtained by assembling in vitro various elements in order to form a neo-organ which is introduced preferably in the peritoneal cavity of the recipient. The implant comprises a biocompatible support intended to the biological anchoring of cells; cells having the capacity of expressing and secreting naturally or after recombination a predetermined compound, for example a compound having a therapeutical interest; and a constituent capable of inducing and / or promoting the geling of said cells. The invention also relates to a kit for the preparation of the implant as well as to a new recombinant retroviral vector comprising a provirus DNA sequence modified in that the genes gag, pol and env have been deleted at least partially so as to obtain a proviral DNA capable of replication. The invention also relates to recombinant cells comprising the new retroviral vector.

Description

[0001] The invention relates to a biocompatible implant for the expression of defined substances in man or in animals, in particular for the anchoring of the recombinant cells at the invention.[0002] The present invention also relates to retroviral vectors for the preparation of recombinant cells capable of being implanted in vivo for a therapeutic purposeSTATE OF THE ART[0003] The in vivo introduction of implants capable of expressing defined substances for example for therapeutic purposes necessitates the use of efficacious agents as regards the desired therapeutic or prophylactic objective and that the organism into which the implant is introduced has the capacity to tolerate it in the relatively long-term.[0004] The earlier international patent application published under the number 92 / 15676 described agents to obtain in vivo the expression of defined nucleotide sequences for the purpose of a therapeutic treatment of diseases resulting from a genetic anomaly. This international ...

AI Technical Summary

Benefits of technology

[0035] Advantageously, the implant such as described above comprises in addition a growth factor, for example the bFGF (basic Fibroblast Growth Factor). This growth factor promotes the vascularization of the neo-organ when the latter is implanted in vivo.

[0050] The implant thus constituted allows the in vivo formation of an individualized and, if necessary, stable neo-organ in which the biological support is capable of being progressively resorbed leaving in place a structure containing a vascularized connective tissue of a form quite comparable to that of the implant, this neo-organ having however, optionally a reduced volume compared with the volume of the original implant.

[0059] This agent contributes to the stable binding of the angiogenic factors to the support of biological origin of the implant.

[0061] Heparin and its derivatives are capable of binding to the constituents promoting gelation and thus of increasing the affinity of the angiogenic factors for the constituents responsible for gelation. In particular, heparin binds to collagen and thus increases the affinity of bFGF for collagen.

[0068] The agents described in the invention thus make it possible to envisage the treatment of genetic or acquired diseases over a long period, more than several months, and do so without the repeated administration of the expression product of the exogenous nucleotide sequence whose therapeutic activity is desired Furthermore, the agents described in the invention lead to the production in the form of a secreted protein of a quantity of expression product of the exogenous nucleotide sequence sufficient to have a therapeutic effect in vivo.

[0080] The kit may also contain cells having the capacity to express and secrete naturally or after recombination a defined substance, far example a substance of therapeutic interest. this deletion makes it possible to diminish and preferably to neutralize the transcriptional effect of the LTR region by conserving the capacity of the exogenous promoter to promote and control the expression of the exogenous nucleotide sequence contained in the retroviral vector.

Problems solved by technology

However, such a deletion has the disadvantage of being accompanied by a considerable diminution of the vector titers.

This defective or insufficient expression results from the nature of the cell or occurs because of a disease affecting this cell in a given individual.

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