Antibiotics

• Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, today reported initial clinical data about SER-155.
• Enrollment in the placebo-controlled Cohort 2 portion of the study is ongoing and topline results are anticipated in mid-2024.
• The SER-155 Phase 1b study includes two cohorts, with Cohort 1 designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the gastrointestinal tract.
• ET to discuss Q1 2023 financial results and provide a business update, including a discussion of new SER-155 study results.

• Due to its cost-effectiveness and affordable alternative the Generic Sterile Injectables market is likely to expand in coming years.
• However, the increased demand for critical care medications, including sterile injectables, due to the surge in COVID-19 cases created opportunities for manufacturers of generic sterile injectables.
• Key questions answered in this report:
  What is the current size of the generic sterile injectables market, and what is the projected market growth rate?
• What is the competitive landscape of the generic sterile injectables market, and what are the market shares of key players in the industry?

• Some research on emerging viruses can result in variants that gain the ability to infect people but this does not necessarily mean the research is dangerous or that it is not fruitful.
• Concerns have focused on lab research on the virus that causes bird flu in 2012 and on the virus that causes COVID-19 since 2020.
• Clarifying what gain-of-function research really is can help clarify why it is an essential scientific tool.

What is gain of function?

• To study how a living thing operates, scientists can change a specific part of it and then observe the effects.
• These changes sometimes result in the organism’s gaining a function it didn’t have before or losing a function it once had.
• This mutated immune cell, called a CAR-T cell thereby “gains the function” of being able to bind to cancerous cells and kill them.

Medical advances from gain-of-function research

• Only decades later does the research bring a new treatment to the clinic or a new technology within reach.
• The development of most antibiotics have relied on the manipulation of bacteria or mold in gain-of-function experiments.
• Alexander Fleming’s initial discovery that the mold Penicillium rubens could produce a compound toxic to bacteria was a profound medical advance.
• Gain-of-function research in virology has also been critical to the advancement of science and health.

Nature’s gain-of-function experiments

• Many viruses that infect such nonhuman animals as bats, pigs, birds and mice have the potential to spill over into people.
• Gain-of-function experiments in the lab can help scientists anticipate the changes viruses may undergo in nature by understanding what specific features allow them to transmit between people and infect them.
• In contrast to nature’s experiments, these are conducted in highly controlled lab conditions designed to limit infection risk to laboratory personnel and others, including air flow control, personal protective equipment and waste sterilization.
• Scientists have a better appreciation of the tangible risk of bird flu spillover because of gain-of-function experiments published a decade ago.

Oversight on gain of function

• Many researchers would likely agree that gain of function as a general tool is an important way to study biology that should not be restricted, while also arguing that it should be curtailed for research on specific dangerous pathogens.
• While updates to current oversight are not unreasonable, we believe that blanket bans or additional restrictions on gain-of-function research do not make society safer.
• Clarifying which specific research areas are of concern regarding gain-of-function approaches can help identify how the current oversight framework can be improved.

• These metabolites provide the microbes major evolutionary advantages, such as allowing them to interact with one another or their environment and helping defend against different threats.
• Because of the diverse functions bacterial natural products have, many have been used as medical treatments such as antibiotics and anti-cancer drugs.
• By generating previously unknown chemical compounds from the reconstructed genomes of ancient bacteria, our newly published research provides a proof of concept for the potential use of fossil microbes as a source of new drugs.

Reconstructing ancient genomes

• Such genes are difficult to detect and reconstruct from ancient DNA because very old genetic material breaks down over time, fragmenting into thousands or even millions of pieces.
• We sequenced billions of such ancient DNA fragments, then improved a bioinformatic process called de novo assembly to digitally order the ancient DNA fragments in stretches of up to 100,000 nucleotides long – a 2,000-fold improvement.
• This cluster bore the molecular hallmarks of very ancient DNA and belonged to the bacterial genus Chlorobium, a group of green sulfur bacteria capable of photosynthesis.
• By reconstructing these ancient compounds, our findings highlight how archaeological samples could serve as new sources of natural products.

Mining ancient natural products

• Because the environments they inhabit today differ from those of their ancestors, microbes today likely produce different natural products than ancient microbes from tens of thousands of years ago.
• Human lifestyles also dramatically changed over this transition as people began living outside of caves and increasingly experimented with food production.
• By reconstructing microbial genomes from archaeological samples, scientists can tap into the hidden diversity of natural products that would have otherwise been lost over time, increasing the number of potential sources from which they can discover new drugs.

Scaling up ancient molecules

• To tap into the vast diversity of chemical compounds encoded in ancient DNA, we now need to streamline our methodology to be less labor-intensive.
• We are currently optimizing and automating our process to identify biosynthetic genes in ancient DNA more quickly and reliably.
• Although we can recreate ancient molecules, their biological and ecological roles are difficult to decipher.
• Whether or not the functions of these compounds have remained the same in the modern relatives of ancient microbes remains to be tested.