Deep learning algorithms have enabled the discovery of molecular structures of interest in biomedicine to design treatments against aggressive diseases such as idiopathic pulmonary fibrosis (IPF). Scientists at Insilico Medicine Inc. selected a target for IPF using artificial intelligence (AI), then designed an inhibitor to block it, and tested it in vitro, in vivo, and in clinical trials.
One topic at the 31st Conference on Retroviruses and Opportunistic Infections (CROI 2024) held in Denver this month was that resistance to antiretroviral therapy (ART) has become a public health problem for people living with HIV. Without a vaccine or a cure, these patients depend on treatments that suppress viremia by preventing the virus from replicating. They are lifelong treatments and, until new advances succeed in eradicating the virus from reservoirs, the only option available.
Overall, the story of HIV is one of astounding success. But to declare victory, it will be necessary to develop a vaccine. The opening session of the 31st Conference on Retroviruses and Opportunistic Infections (CROI) 2024 looked back to the failures but also the advances in research, all the steps that over the years brought the basic science knowledge that could bring an HIV vaccine in the future. This year, the former director of the Viral Pathogenesis Laboratory at the NIAID Vaccine Research Center, Barney Graham, was named for the Bernard Field Lecture, where he presented “Modern vaccinology: a legacy of HIV research.”
An Italian group of researchers has used zinc finger editing to silence the PCSK9 gene and improve blood cholesterol levels in mice by applying a single dose of their modifier. The epigenetic-based method could be an alternative to genome editing.
Bruton tyrosine kinase (BTK) enzyme inhibitors used to treat B-cell cancers, including chronic lymphocytic leukemia and non-Hodgkin lymphoma, also produce resistance by causing mutations in the protein. Now, a study on the BTK degrader NX-2127 showed the compound could be effective in eliminating BTK regardless of its mutations.
Using interactions between viral peptides and human proteins as a starting point, researchers from Enyo Pharma Inc., the University of Lyon and other institutions were able to bootstrap themselves to a mitochondria-targeting small molecule that showed activity in a mouse model of nonalcoholic steatohepatitis (NASH) with chronic kidney disease.
The field of peptides is exploding, Perpetual Medicines Corp. co-founder, chairman and CEO Kerry L. Blanchard recently told BioWorld, “with a projected growth rate far surpassing large and small molecules, and gene therapies. The area is underinvested, too, so this is a good opportunity to focus on peptide therapeutics.”
If we unraveled the DNA of the 46 chromosomes of a single human cell, it would barely measure 2 meters. If we did the same with the rest of the body, if we aligned the 3 billion base pairs of its 5 trillion cells, we could travel the distance from the Earth to the Sun more than 100 times. It seems unreachable. However, that is the unit of knowledge of the large sequencing projects achieved in 2023. From the generation of the human pangenome to cell-by-cell maps of the brain and kidneys, scientists this year have completed several omics collaborative projects stored in large international databases. Now, what’s the plan?
Modifying a patient’s DNA is no longer just for science fiction novels. The CRISPR gene editing technique developed by Jennifer Doudna and Emmanuelle Charpentier only took 10 years to reach the market as Casgevy (exagamglogene autotemcel/exa-cel, Vertex Pharmaceuticals Inc.), treating congenital pathologies such as β-thalassemia and severe sickle cell disease. But science does not stop.
Artificial Intelligence (AI) driven tools have the ability to design new drugs, with a bit of help from humans, said Anders Hogner, from Astrazeneca plc’s R&D department at the Bio-IT World Conference & Expo Europe in London. “We don’t have anything out there yet,” he added, but the company appears to be working on it.