Gene delivery by microneedle injection

• US 6,090,790 A
• Filed: 12/15/1997
• Issued: 07/18/2000
• Est. Priority Date: 12/14/1989
• Status: Expired due to Fees

• Current Assignee: Applied Tissue Technologies LLC
• Original Assignee: Elof Eriksson
• Inventors: Eriksson, Elof
• Primary Examiner(s): Chambers, Jasemine
• Assistant Examiner(s): FALK, ANNE MARIE
• Application Number:
  US08/990,442
• Time in Patent Office: 946 Days
• Field of Search: 435/455, 514/44, 604/46
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 Bones
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 37/0076 Tattooing apparatus apparatus for marking animals A01K11/00; vaccine applicators having needles or other puncturing means A61B17/205
• CPC Class Codes: A61M 39/0247 Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body peritoneal dialysis catheters A61M1/285; tracheostomy devices A61M16/0465; measuring pressure within the body A61B5/03; colostomy devices A61F5/445; gastrotomy feeding tubes A61J15/0015; means for fixing a feeding tube outside of the body A61J15/0053
• CPC Class Codes: A61M 5/3287 Accessories for bringing the needle into the body; Automatic needle insertion A61M5/20, A61M5/31525 take precedence
• CPC Class Codes: A61M 5/3298 : Needles arranged in parallel
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 5/0629 : Keratinocytes; Whole skin

Abstract

Direct gene transfer of genetic material into an external or internal target cell site ("microseeding"), in optional combination with a wound treatment chamber, are particularly effective as a means of obtaining long term expression of native or non-native polypeptides in a host. A wide variety of proteins and materials can be expressed, either for secretion into the general blood and lymphatic system, or to alter the properties of the protein, for example, to not express proteins eliciting an immune response. The use of the optional wound chamber system for gene transfer to skin target sites also allows non-invasive assessment of the success of transfer by assaying for the presence of the expressed protein in wound fluid, in contrast to the prior art use of invasive techniques, such as biopsies, in order to achieve the same assessment of early expression.

Claims

1. A method for introducing expressible genetic material into a periosteal cell, the method comprising the step of:

repeatedly injecting the genetic material into periosteal tissue at an in situ site on a human or non-human animal with a microneedle, whereby the genetic material is taken up by periosteal cells and expressed therein and whereby a change in the animal attributable to the expression of the genetic material is detectable.

2. A method as claimed in claim 1 wherein the genetic material encodes a product selected from a group consisting of a bone morphogenetic protein, a cytokine, a leukemia inhibitory factor, oncostatin-M, cardiotrophin-1, an interleukin, a PDGF, an IGF, an FGF, TNF-alpha, GM-CSF, EGF, HG-EGF, VEGF, IP-10, PF-4, MCP-1, HGF, RANTES, a prostaglandin, decorin, a variant thereof, and a combination thereof.

3. A method for stimulating bone growth, the method comprising the step of repeatedly injecting expressible genetic material that encodes bone morphogenetic protein 2 (BMP-2) into periosteal tissue in a human or non-human animal with a microneedle, whereby the periosteal cells take up and express BMP-2 therein and then secrete BMP-2 to stimulate the growth of the bone.