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Patent Issued for Mussel Adhesive Protein Derived Vectors for Gene Delivery

May 29, 2014



By a News Reporter-Staff News Editor at Gene Therapy Weekly -- From Alexandria, Virginia, NewsRx journalists report that a patent by the inventors Hwang, Dong Soo (Pohang, KR); Cha, Hyung-Joon (Pohang, KR), filed on December 29, 2008, was published online on May 13, 2014 (see also Postech Academy-Industry Foundation).

The patent's assignee for patent number 8722617 is Postech Academy-Industry Foundation (Pohang, KR).

News editors obtained the following quote from the background information supplied by the inventors: "This invention relates to gene delivery and gene therapy. More particularly, the invention relates to compositions and methods for use, and making thereof, for delivering nucleic acids as genomic DNA, RNA, or any nucleic acid analogue, including but not limited to aptamer, for life science applications, or other non-soluble bioactive molecules such as protein, peptides or small non-soluble drugs.

"There are a number of techniques for the introduction of genes into cells. One common method involves viruses that have foreign genes (e.g., transgenes) incorporated within the viral DNA. However, the viral genes are also delivered with the desired gene and this can lead to undesirable results.

"To address some problems encountered in viral vectors, non-viral gene delivery systems such as cationic liposomes or synthetic gene carriers have been widely sought as alternatives and investigated intensively.

"The carrier molecules bind and condense DNA into small particles which facilitate DNA entry into cells through endocytosis or pinocytosis. In addition, the carrier molecules act as scaffolding to which ligands may be attached in order to achieve site specific targeting of DNA.

"The most commonly used DNA condensing agent for the development of non-viral gene delivery systems is polylysine in the size range of dp 90-450. Its amino groups have been derivatized with transferrin, glycoconjugates, folate, lectins, antibodies or other proteins to provide specificity in cell recognition, without compromising its binding affinity for DNA. However, the high molecular weight and polydispersity of polylysine also contribute to a lack of chemical control in coupling macromolecular ligands which leads to heterogeneity in polylysine-based carrier molecules. This can complicate the formulation of DNA carrier complexes and limits the ability to systematically optimize carrier design to achieve maximal efficiency.

"In general, polycationinic polymers are known to be toxic and the PLL backbone is barely degraded under physiological conditions. It will remain in cells and tissue which can cause undesirably high toxicity.

"Biodegradable polymers, such as polylactic/glycolic acid (negatively charged), and polylactide/glycolide (neutral) have been used as gene carriers in the form of non-soluble particulates.

"Cationic liposomes are commercialized non-viral carriers due to their non-immunogenicity and simplicity of large-scale production. However, their efficiencies can be relatively low due to inactivation by serum or blood components and loose condensation of DNA associated with decreased uptake into cells.

"To overcome the problems of liposomes, polymer systems or cationic proteins have been introduced. The cationic protein-based gene delivery system has several advantages, including ease of use in serum- and/or antibiotic-containing medium, the ability to target nucleic acids to specific cell types, no limit on the size or type of target nucleic acid, possibility of modular attachment of targeting ligands, and the potential for cost-effective, large-scale manufacture.

"A number of histone proteins have been widely analyzed as potential gene delivery materials. Histones display similar or higher transfection efficiency in mammalian cells, compared to the widely used transfection agent, Lipofectamine (Jung et al., Biotechnol. Prog. vol 24. pp 17-22, 2008). Histones are basic proteins that contain several lysines and arginines. These positively charged amino acids facilitate electrostatic interactions with the negatively charged phosphate backbone of DNA. However, application of eukaryotic histones for gene delivery is limited by low recombinant expression levels and infection risks.

"The invention aims at eliminating some of the major disadvantages and limitations of the known techniques described above. Firstly, it aims at providing a gene carrier that is non toxic, biodegradable, and/or biocompatible. Secondly, it provides a gene carrier composition that is efficient and viable under in vivo conditions such as serum condition."

As a supplement to the background information on this patent, NewsRx correspondents also obtained the inventors' summary information for this patent: "It is an object of the present invention to provide a composition and a method for delivering a nucleic acid into a cell.

"It is also an object of the present invention to provide a biocompatible and biodegradable gene delivery composition and methods of use and making thereof.

"It is yet another object of the invention to provide a non-toxic, soluble, biodegradable, non-viral composition and a method of use thereof, for delivering exogenous nucleic acids into a targeted cell.

"These objects can be achieved by providing a cationic protein, mussel adhesive protein.

"In an embodiment of the present invention, it is to provide a method for delivering a nucleic acid sequence into eukaryotic cells comprising contacting the cells with a mixture of the nucleic acid sequence and a gene-delivering peptide comprising a peptide derived from a mussel adhesive protein.

"In another embodiment, it is to provide a method of delivering a selected nucleic acid into a selected cell comprises the steps of:

"(a) mixing an effective amount of the selected nucleic acid with an effective amount of mussel adhesive protein to form a complex;

"(b) contacting the selected cell with the complex under the conditions that the nucleic acid and the gene-delivering peptide are delivered across the cell membrane."

For additional information on this patent, see: Hwang, Dong Soo; Cha, Hyung-Joon. Mussel Adhesive Protein Derived Vectors for Gene Delivery. U.S. Patent Number 8722617, filed December 29, 2008, and published online on May 13, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=87&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=4316&f=G&l=50&co1=AND&d=PTXT&s1=20140513.PD.&OS=ISD/20140513&RS=ISD/20140513

Keywords for this news article include: Biotechnology, Peptides, Proteins, Liposomes, Polylysine, Amino Acids, DNA Research, Gene Therapy, Bioengineering, Drug Delivery Systems, Postech Academy-Industry Foundation.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Gene Therapy Weekly


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