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Recently, researchers from the Broad Institute of MIT and Harvard University published a research paper titled "Systematic multi-trait AAV capsid engineering for efficient gene delivery" in Nature Communications. The study developed a general machine learning method for systematically designing multi-feature AAV capsids, Fit4Function, which generates reproducible screening data by utilizing AAV capsid libraries that uniformly sample the manufacturable sequence space to train accurate sequence-to-function models, thereby helping to design AAV protein shells (capsids) with multiple ideal features, such as the ability to deliver genes to specific organs or achieve gene delivery in multiple species, thereby helping to accelerate the engineering of AAVs for gene therapy.
Recombinant adeno-associated virus (rAAV) vector is one of the most promising viral vectors in gene therapy. Currently, three-plasmid transfection based on human embryonic kidney 293 (HEK293) cells is the most commonly used rAAV vector production system, but its low production efficiency has become one of the challenges faced by rAAV gene therapy drugs on the road to commercialization. In view of this challenge, researchers are working to develop improved methods to increase the production of rAAV in HEK293 cells.
On August 14, 2024, the World Health Organization (WHO) announced that the monkeypox (mpox) outbreak in parts of Africa constitutes a "Public Health Emergency of International Concern" (PHEIC). This is the second time in two years that the WHO has declared a monkeypox outbreak a PHEIC event. PHEIC is the highest alert level under international health law. The WHO said that the monkeypox outbreak has the potential to spread further in Africa and to other continents. According to a report released by the Africa Centers for Disease Control and Prevention, from the beginning of this year to July 28, the number of new monkeypox cases in Africa has surged by 160% compared with the same period last year. So far, 34 African countries have reported the discovery of the disease or have been identified as "high-risk" countries.
Respiratory syncytial virus (RSV) causes a significant disease burden in the global population, with an estimated 33.1 million cases each year, and is the leading cause of bronchitis and viral pneumonia in infants. It particularly affects children and the elderly, and treatment options are limited and relatively ineffective.
Adeno-associated virus (AAV)-based viral vectors used in human gene therapy can induce innate immune pathways, leading to the initiation of the body's adaptive immune response. Recently, in a review article entitled "Innate Immune Sensing of Adeno-Associated Virus Vectors" published in the international journal Human Gene Therapy, scientists from Indiana University and other institutions described the range of possible redundant innate immune pathways that AAV vectors can activate, which will lead to excessive adaptive immune responses.
Gene replacement using adeno-associated virus (AAV) vectors is a promising approach to treat many diseases. However, the packaging capacity of AAV (about 4.7 kilobases) poses a challenge to this treatment modality, limiting its application in diseases associated with larger protein coding sequences (such as the 14 kilobases of mRNA in Duchenne muscular dystrophy).
Spastic hereditary paraplegia type 50 (SPG50) is a typical ultra-rare disease (incidence is less than 1 in 50,000). The disease is caused by biallelic pathogenic variants in the AP4M1 gene, which encodes a subunit of the AP-4 protein complex. It is a progressive neurodegenerative disease. Patients usually begin to show symptoms in infancy, resulting in developmental delay, speech disorders, epileptic seizures, and gradual paralysis of the limbs. In their teens, most patients are wheelchair-dependent and show severe cognitive impairment, usually dying in adulthood.
Recently, researchers from Yale University and other institutions published a research paper titled "In vivo AAV-SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy" in the journal Nature Biotechnology. After years of technical research, the research team used the AAV-transposon system to integrate the CRISPR library into the genome, overcoming the obstacles of low efficiency of primary NK cell transduction and gene editing. Through four parallel CRISPR screening experiments and single-cell sequencing data, the study discovered a new target, CALHM2, which provides a new therapeutic target for NK cell tumor immunity.
As understanding of immune activity at the tumor site increases, immunotherapy has received widespread attention as an effective cancer treatment strategy, leading to a major shift in cancer research and clinical trials. The main purpose of tumor immunotherapy is to stimulate host anti-tumor immunity, establish an immune-sensitive microenvironment, and ultimately achieve tumor shrinkage while improving the overall survival rate of patients.
Researchers from Shanghai Jiao Tong University in China recently published a research paper titled "Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers" online in Nature Biomedical Engineering. This study reports the design and performance of a virus-like particle targeting dendritic cells (DCs). The particles feature the Sindbis viral glycoprotein engineered to recognize surface proteins on DCs and package mRNA encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein or herpes simplex virus 1 glycoproteins B and D.
