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Bejamine Deverman's team at the Broad Institute recently published a research paper titled "An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery" online in Science. The study designed an AAV capsid, BI-hTFR1, that binds to the human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). Compared with AAV9, BI-hTFR1 has a higher active transport capacity across the human brain endothelial cell layer and provides a 40-50-fold enhancement of reporter gene expression in the CNS of mice carrying a human TFRC knock-in. This enhanced tropism is CNS specific and is not present in wild-type mice.
Recently, Xiamen University in China published a research paper titled "Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects" in the journal Signal Transduction and Targeted Therapy. This study developed an oncolytic virus, rVSV-LCMVG, that is less likely to induce virus-neutralizing antibodies, and further confirmed that the oncolytic virus can enhance the anti-tumor effect when used in combination with adoptive transfer of T cells or mRNA cancer vaccines.
Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that affects the mucosa of the oral cavity, nasal cavity, and throat. Its occurrence is often associated with tobacco exposure, alcohol abuse, and viral infections. Currently, researchers are unclear about the association between human papillomavirus (HPV) infection status and molecular characteristics of HNSCC.
Oncolytic viruses (OVs) are a type of natural or recombinant viruses that can selectively infect and kill tumor cells without damaging normal cells. Oncolytic viruses have the advantages of good targeting, few adverse reactions, multiple ways to kill tumors, and are not prone to drug resistance. And oncolytic virus combined with chemotherapy, radiotherapy and immunotherapy has a synergistic effect. In recent years, with the continuous development of technology and the deepening of research, the selectivity and effectiveness of oncolytic virus products on tumor cells have been continuously improved, while the impact on normal cells has been further reduced, and they have gradually become a research and development hotspot.
Bacterial infections can lead to the formation of abscesses, pockets of dead cells and debris surrounded by inflammatory immune cells. Bacteria can multiply in an abscess and cause more infections, further damaging surrounding tissue. In severe cases, these immune responses can spread throughout the body and eventually cause life-threatening organ failure or sepsis. But how these abscesses form and how to prevent them have not been better understood.
Understanding how the virus spreads in the human body is critical to developing effective drugs and treatments to stop its spread. In a new study, researchers from the Texas Biomedical Research Institute have found that the Ebola virus (EBOV) can build and use intercellular tunnels to move from one cell to another, thereby evading treatment. Relevant research results were recently published in the Journal of Infectious Diseases, with the title of "Ebola Virus Uses Tunneling Nanotubes as an Alternate Route of Dissemination."
Mice enter their twilight years at around two years of age, which is roughly equivalent to 80 years in humans. When scientists introduce specific mutated genes into mice and age them over time, the mice become forgetful and irritable, eventually displaying the same symptoms of Alzheimer's disease that many older adults experience.
David Liu's team from the Broad Institute in the United States published a research paper titled "Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo" in the journal Nature Biotechnology. This study developed prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. The researchers systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to PE-eVLP constructs based on previously reported base editor eVLP architectures. And achieved in vivo base editing and restored partial visual function in two mouse models of genetic blindness.
The downstream processes of AAV production mainly include: cell lysis and clarification, viral vector purification (capture purification, fine purification, ultrafiltration concentration, etc.), formulation/canning, and quality testing.
Gene therapy was born to treat genetic diseases, but with the development of technology, in recent years it is going beyond the scope of treating genetic diseases and gradually entering the field of major non-genetic diseases, and even the field of solid tumors. As the field of AAV gene therapy grows, its upstream and downstream production links also need to be improved. The entire industrial production process of AAV gene therapy products can be roughly divided into three parts: upstream culture, downstream purification and finished product packaging. Among them, upstream culture and downstream purification involve more production steps and the technology is more complex. Next, let us go into the upstream of AAV industrial production to find out!
