Optimized gene therapy of Parkinson's disease shows great success

Levodopa is a commonly-used drug to alleviate the symptoms of Parkinson's disease. However, patients taking the drug mostly feel disappointed as the final outcome. When initially taking levodopa, the patient's symptoms in the tremor and balance would be mitigated and controlled. But as time goes on, the effect of drugs will become increasingly worse. They may have to use ultra-high doses of the drug, and some patients may spend several hours in a paralyzed state in almost every day.

Today, Voyager Therapeutics Company located in Cambridge, Massachusetts thought that gene therapy can prolong the efficacy of the drug levodopa. Currently, the company's gene therapy has entered clinical trials with the aid of recombinant proteins such as recombinant mouse proteins.

Parkinson's disease is due to the death of neuron which produces dopamine in brain, resulting in difficulties of patients in athletic ability. People plagued by this disease include the famous boxer Muhammad Ali and actor Michael Fox. Although the reason leading to the death of brain dopamine neuron is still not fully understood by scientists, the reason for the failure of the drug levodopa has been found. Levodopa is the precursor of dopamine. It can be turned into dopamine under the disposal of aromatic L- amino acid decarboxylase (AADC) in the brain. However, in the brain of patients with Parkinson's disease, with the passage of time, AADC levels are decreasing. This results the condition that L-dopa can't be sufficiently converted to dopamine.

The strategy of Voyager wishes to inject adeno-associated virus (AAV) which expresses AADC into the patient's brain through gene therapy, thereby restoring AADC levels in the brains of patients and prolonging the efficacy of levodopa. "We have spent 60 years to study the pharmacology of dopamine," said Steven Paul, CEO of Voyager. "If we can put genes into the right brain tissues at the right time, then there is no reason that we don't succeed."

However, to put the correct gene into the right brain tissue to ensure a sufficient number of expressions is not an easy task. In order to ensure that AADC can express in the correct tissue, Voyager specially designed an injection system which can put the virus carrying AADC gene into the brain. In recent clinical trials, the patients will lie on the MRI machine to accept injection of the virus. Thus, brain surgeon can see the position of the putamen in the brain, thus ensuring the injected virus can cover this important area which needs AADC protein expression. Meanwhile, Voyager Company adds a chemical marker on AADC protein so that the doctor can see the position of proteins which express in the brain after surgery. In ongoing clinical trials, the gene therapy of Voyager has shown a significant effect on some patients.

Dr. Krystof Bankiewicz, one of the co-founders of Voyager said, "We think the failure of previous gene therapy of Parkinson's disease is that the method of gene transfer has not been optimized." Whether the optimized gene therapy of Voyager Company would succeed? We look forward to seeing the results of their clinical trials. Flatebio offers recombinant proteins of good quality like recombinant Cdh4 at competitive prices.

Get to know what cytokine recombinant protein is

Cytokine (CK) refers to a class of small molecular proteins which are synthesized and secreted by immune cells (e.g. mononuclear - phagocytic cells, T cells, B cells, NK cells, etc.) and certain non-immune cells (e.g. vascular endothelial cells, epidermal cells, fibroblasts, etc.) via being stimulated and it has a wide range of biological activity. It belongs to recombinant protein with high purity, high activity and low endotoxin features, and it includes recombinant human protein, recombinant mouse protein and recombinant dog protein.

Cytokines can be divided into the following categories by function:

1. Interleukin (IL)

This is a class of cytokines produced by a variety of cells and acts on a variety of cells. It originally got the name because it is produced by white blood cells and plays a role in leukocytes and now it continues to use this name.

2.Interferon (IFN)

It is named because of its ability of interfering with viral replication. It has a very wide range of biological activity and plays an important role in the immune response and immune regulation. It is one of the major pro-inflammatory cytokines. Interferon is divided into: I type (seven kinds, such as IFN-α and IFN-β) and type II (only IFN-Y).

3. Tumor necrosis factor (TNF)

It is named because it can both directly kill tumor cells in vitro and in vivo. There are about 30 members in his family. Its main members include: TNF-α, a single-core factor mainly by monocytes and macrophages; TNF-β, one kind of lymphokines and it is mainly produced by lymphocytes and NK cells produce, and its biological activity is similar to TNF -α.

4. Colony stimulating factor (CSF)

A group of cytokines in vivo and can selectively stimulate hematopoietic progenitor cells to proliferate, differentiate and form a cytokine lineage cell colonies, including macrophages CSF, granulocyte CSF, macrophage / granulocyte CSF and stem cell factor.

5. Growth factor (GF)

A class of cytokines which can mediate different types of cell growth and differentiation. According to their function and different the cellular effects, they are named as transforming growth factor (TGF), nerve growth factor (NGF), epidermal growth factor (EGF), vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF) and the like.

6. Chemokine

A class of cytokine family which has different target cells chemotactic effect and can be secreted by certain white blood cells and tissue cells. It is a family of proteins including more than 60 members. Most members contain four conserved cysteine (C). According to its N-terminal cysteine arrangement, it can be divided into four subfamilies: CXC, CC, C and CX3C.

You can visit Cusabio’s website to find more recombinant proteins.

Ten most popular databases of protein research

Previously/Before then, GEN website made a list of the most popular databases of protein research. See detailed list of the following:

1. BioGRID database was established in 2003. It is a database about protein - protein interactions and gene interaction database. Some wonderful studies on recombinant mouse protein also come from here.

2. DDBJ database was established in 1984. It is one of the world's three major DNA databases. Together with the NCBI's GenBank and EBI EMBL database, they compose of international DNA databases which updates daily exchange of data and information.

3. Database of Interacting Proteins is a database records protein - protein interactions which have been experimentally determined. This database is intended to provide a comprehensive and integrated tool for the scientific community to browse and efficiently extract protein interactions related to biological processes for network information interaction. In addition to details of cataloging protein - protein interactions, DIP is also useful for understanding protein function and protein - protein relationship, studying the properties of protein interaction networks, predicting benchmarking protein - protein interaction and studying the evolutionary of protein - protein interactions.

4. ExPasy database collects a lot of information, providing a range of tools and links for biologists to solve the puzzle of the information age.

5. Gepasi database is a modeling software about biochemical systems. It simulates the kinetics systems of biochemical reactions and provides a number of tools to model data to perform metabolic control analysis and linear stability analysis.

6. IntAct database provides a free, open-source analysis tool for intermolecular interactions.

7. KEGG database is an utilities repository with advanced features which helps to understand biological systems.

8. MINT is a database about molecular interactions. Data sources are mainly from scientific literature related to verification of protein - protein relatio.

9. SWISS-PROT is annotated protein sequence database and maintained by the European Bioinformatics Institute (EBI).

10. Uniprot database provides comprehensive and high-quality information of protein sequence and protein functions for the scientific community and it also offers them with some technologies of recombinant proteins.

Chinese scientists release new findings of mTORC1 protein complex

Cells would strictly control their metabolic processes to reconcile their growth and nutritional status according to nutrient levels in the environment. mTORC1 (mammalian target of rapamycin complex) is responsible for the integration of environmental and intracellular signaling and is responsible for the regulation of cell growth. mTORC1 is similar to the generation of recombinant human protein. mTORC1 dysregulation is very common in cancer, diabetes and other human diseases.

Amino acids will make mTORC1 transfer to the lysosome and activate there. People used to think that this activation is dependent on the amino acid Rag small GTPase, Ragulator complexes and v-ATPase (vacuolar H + -adenosine triphosphatase).

Research team from Fudan University and the University of California recently found that different amino acids on the regulation of mTORC1 are not the same. Leucine mTORC1 activation requires Rag GTPase, but activation of glutamine does not depend on Rag GTPase. The results were published in journal Science on January 7, and the paper's corresponding author is famous scholar professor Kun-Liang Guan.

Professor Kun-Liang Guan is mainly engaged in signal transduction regulating cell growth and tumor cell biology. He has been awarded many honors including the "MacArthur Genius Award" in United States. He is now currently a professor at the University of California, San Diego (UCSD) Department of Pharmacy, Institute of Life Sciences, Zhejiang University jointly Dean, Fudan University Biomedical Institute for Genomic Research laboratory of molecular cell Biology and PI.

The researchers knocked out cells RagA and RagB, but glutamine still allows mTORC1 to transfer to lysosomes. The study shows that this process requires v-ATPase but not Ragulator. In addition, the researchers also found that glutamine-induced activation of mTORC1 needs Arf1 GTPase to play a role.

This study reveals an mTORC1 activation cascade which is not dependent on Rag GTPase, showing the specific amino acid differences in the regulation of mTORC1. The article points out that leucine needs RagA and RagB to activate mTORC1, while glutamine doesn't need them. This difference appears to be an evolutionarily conserved regulation.

There are many cancer cell lines show increase of mTORC1 activity, and the growth of cancer cells is highly dependent on glutamine. It can be seen that mTORC1 activation induced by glutamine plays an important role in the growth of normal cells and tumor cells, was also occupied in the study and development of recombinant mouse protein.