亚洲知识产权资讯网为知识产权业界提供一个一站式网上交易平台,协助业界发掘知识产权贸易商机,并与环球知识产权业界建立联系。无论你是知识产权拥有者正在出售您的知识产权,或是制造商需要购买技术以提高操作效能,又或是知识产权配套服务供应商,你将会从本网站发掘到有用的知识产权贸易资讯。

Aptamers that promote neuronal growth by binding to and blocking the protein Nogo

技术优势
1. Stability of DNA aptamers over protein enables better storage and long shelf-life 2. Cost-effective synthesis of DNA aptamers via efficient chemistry in large quantity, 3. Low-toxicity of DNA clearance by the body without affecting the liver 4. Higher-absorption of aptamers efficiently crossing the blood-brain barrier compared to antibody therapy
详细技术说明
Damaged axons resulting from central nervous system disorders or injuries cannot regenerate because inhibitor proteins block axon regrowth. One such protein is Neuronal Growth Inhibiting Protein (Nogo), which binds to its receptor (NgR1) and induces breakdown of growth cone components thereby inhibiting axon growth. Pharmaceutical companies are developing and testing antibodies against receptor NgR1 to treat a range of disorders including spinal cord injury, stroke, ALS, and MS. These antibody proteins, however, may be unstabile, costly to synthesize and purify, and have low absorption. Alternatively, recent research describes using short RNA/DNA molecules called aptamers to block inhibition of neuron growth. The inventors discovered that single-stranded DNA aptamers effectively disrupt Nogo binding to NgR1, which increases neuron outgrowth and permits axonal repair. These aptamers were synthesized through a method of systematic evolution of ligands by exponential enrichment (SELEX) involving multiple iterations of selection, amplification, deep sequencing and synthesis of the highest occurring sequence. Some of these aptamers promote axonal growth within a period of days, and the most active aptamer developed can produce neuron growth even in nanomolar concentrations. Use of DNA aptamers may be superior to protein antibodies in terms of increased stability, cost-effective synthesis, and higher absorption in the brain to facilitate treating a range of neurodegenerative disorders.
*Abstract

Neuronal growth inhibiting protein (Nogo), blocks regrowth of damaged neuronal projections (axons) in neurodegenerative disorders. Currently, researchers are developing antibody proteins to inhibit Nogo and produce axon regrowth in a variety of disorders. However, such antibodies are unstable and costly to synthesize. At UCI, the synthesis of nucleic acid molecules called aptamers that selectively bind and block Nogo to promote axonal growth presents a promising alternative pharmaceutical target for treating a range of disorders including spinal cord injury, stroke, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS).

*Principal Investigation

Name: Melanie Cocco

Department:


Name: Andrej Luptak

Department:

其他

State Of Development

In vitro studies have been performed:

§ Functional aptamers that bind Nogo have been selected for and synthesized

§ Aptamer-Nogo binding has been demonstrated to prevent inhibition of neuronal growth in a native lipid environment

§ Functional and active (nanomolar concentrations) aptamers include: Ali3, Ali4+7, Apt3-3, Apt2-2 and Apt2-1

Prospective plans involve testing additional aptamers in neuronal outgrowth and moving to in vivo mouse studies


Related Materials

Alhoshani, A; et. al. Glutamate is a Key Structural Contact Between Nogo-66 and Phosphocholine. BBA – Biomembrane. 2014, 1838, 2350. Link
Vithayathil R; et. al. The Scope of Phage Display for Membrane Proteins. J Mol Biol. 2011, 414, 499. Link
Vasudevan SV; et. al. Protein folding at the membrane interface, the structure of Nogo-66 requires interactions with a phosphocholine surface.Proc Natl Acad Sci. 2010, 107, 6847. Link


Tech ID/UC Case

27175/2015-933-0


Related Cases

2015-933-0

国家/地区
美国

欲了解更多信息,请点击 这里
移动设备