With the explosion of RNA-based therapeutics on the scene, development projects are ramping up to bring these and other nucleic acid-based therapeutics to market. But what exactly are nucleic acid-based drugs and what advantages do they hold over conventional therapeutics (biologics and small-molecule)?

According to Carl Schoellhammer, PhD, principal at DeciBio Consulting, a US-based life science strategy consulting firm, nucleic acid-based therapeutics are drugs that are made up of a string of nucleotides; these include DNA and RNA-based medicines. These types of therapeutics can act at the genetic level to potentially correct or restore healthy function at the level of a patient’s genes.

Vasant Jadhav, PhD, senior vice-president of Research and head of the RNAi Platform group at Alnylam Pharmaceuticals adds that a common feature of nucleic acid-based therapies is that they are “programmable” drugs; a nucleic acid sequence provides the “code” for the intended target. Examples of approved nucleic acid-based therapies include RNA interference (RNAi), antisense oligonucleotides (ASOs), and the now-familiar messenger RNA (mRNA) therapeutics.

RNAi therapeutics utilize a post-transcriptional gene silencing mechanism in which the active ingredient is double stranded short interfering RNA (siRNA). The siRNA targets and degrades mRNA encoded by a disease-causing or disease-associated gene, explains Jadhav. “RNAi therapeutics leverage a naturally occurring protein complex, called RISC [RNA-induced silencing complex], to accomplish gene silencing,” he states.

Meanwhile, ASOs, also a gene silencing medicine, are composed of single-stranded oligonucleotides that hybridize to target RNA and degrade it by “either recruiting RNAseH [ribonuclease H] (so called gapmer design) or modulate splicing to produce desired mRNA (so called splice switching olignucleotides),” according to Jadhav.

Finally, as has been seen with the COVID-19 vaccines, mRNA therapeutics are experimental genetic medicines in which the mRNA itself is the therapeutic entity; it is introduced with the aim of expressing a functional/therapeutic protein or antigen. However, there are currently no approved mRNA therapeutics outside of the COVID-19 vaccines, Jadhav observes.

The COVID-19 vaccines are currently the most well-known type of medicine that utilizes a nucleic acid-based active ingredient (i.e., mRNA). However, as described previously, nucleic acid molecules can be used for other types of medicines (e.g., as gene-silencing medicines).

Schoellhammer emphasizes the fact that nucleic acid-based therapeutics “are a powerful set of medicines with the capacity to turn signals on, or off, at a genetic level.” He points out that there are well over 10 nucleic acid-based therapeutics that are approved by regulators. “These medicines are, broadly speaking, divided by the action they take in the body to either turn signals on or off,” he states.

ASOs, as well as siRNAs, for example, target genes to turn them off or limit their expression. And while most of these approved nucleic acid-based therapeutics are for rare diseases (i.e., small patient population), some have been indicated for vast patient populations: Schoellhammer points to a Novartis product, Leqvio (inclisiran), which received approval by FDA for treating a type of high cholesterol in late 2021 (1).

Inclisiran, Schoellhammer explains, is a siRNA medicine that shuts off a signal in the liver, leading to a lowering of lipids. While it is currently approved for a subsegment of individuals with high cholesterol, he expects that the therapeutic could in the future be applied to anyone with high cholesterol, therefore making these medicines mainstream.

“On the other end of these therapies sits mRNA, which tells the body to produce, or turn on, specific proteins that the mRNA encodes for. [Messenger] RNA is like a blueprint, telling our cells how to make certain proteins. If a certain protein is desired, the corresponding mRNA can be made and delivered so the body will produce it,” Schoellhammer adds.

This is how the COVID mRNA vaccine operates; it is a sequence that encodes for a small fragment of the spike protein in the SARS-CoV-2 virus, for example. “When our body’s cells produce this small protein fragment, they recognize it as foreign, and produce an immune response, just as a traditional vaccine does,” Schoellhammer says.

“The pandemic demonstrated the power of this therapeutic and interest has flourished, with 100s of companies working to create new mRNA-based medicines and well over 200 public programs in development,” Schoellhammer continues. “These programs are tackling a diverse set of applications, ranging from oncology through the development of immune-stimulating treatments to help fight the cancer, to other indications leveraging CRISPR [clustered regularly interspaced short palindromic repeats]-based editing whereby the mRNA encodes for the CRISPR machinery.”

Nucleic acid-based therapeutics hold a definite advantage over conventional biologics or traditional small-molecule APIs. According to Schoellhammer, one of the greatest benefits of nucleic acid-based medicines is their specificity.

“In the case of those that turn off signals, they must find and bind with the exact complementary sequence in our body to turn it off. This means that other genetic signals can be unaffected. Similarly, for mRNA, the sequence, and therefore the protein it encodes for, is controlled. These features greatly limit any off-target effects that are often seen with small molecules or biologics,” Schoellhammer states.

Compared to small molecules and monoclonal antibodies, nucleic acid medicines, such as RNAi therapeutics work “upstream,” asserts Jadhav, treating diseases at their genetic source—that is, at the RNA/transcript level—rather than by addressing the symptoms/manifestations of the disease. Furthermore, Jadhav adds, “small-molecule drugs and monoclonal antibodies have inherent limitations when it comes to the speed with which they can be developed and the type and breadth of diseases they can be used to treat.”

Jadhav points out that the development of small molecules is an arduous process that relies on understanding the structure of the target disease-causing or disease-associated protein (vs. the genetic sequence that encodes that protein). “Oftentimes the structure of the protein is not known and needs to be solved. Identification of the right small molecule requires screening large libraries of chemical compounds to identify a candidate that can interact with the target protein in a ‘lock and key’ fashion. This is a painstaking process that requires extensive trial and error to achieve efficacy, tolerability, and safety,” he emphasizes.

As far as biologics such as antibodies are concerned, Jadhav explains that, while antibodies as a class of medicines have enjoyed much therapeutic success in the past decade, one of the drawbacks here is the inability to access and act on intracellular protein targets. “In contrast to monoclonal antibodies, nucleic acid medicines, such as RNAi therapeutics, can act on disease-causing or disease-associated proteins that are expressed both on the inside and outside of the cell,” he explains.

Meanwhile, Schoellhammer points out a limitation in nucleic acid-based therapeutic development: nucleic acid-based medicines are difficult to deliver, which is a drawback. To work, he specifies, they must be taken up by the right cell in the right place in the body. At the same time, nucleicacid-based medicines are extremely delicate and susceptible to being destroyed in the bloodstream.

“While this can somewhat limit the indications that scientists are using these medicines to treat, it further helps improve these medicines’ specificity and lack of off-target effects. For example, if one uses an siRNA therapeutic to ‘silence’ a target, dosing someone with more of that siRNA should have little effect. This is not the case for small molecules, such as aspirin, where taking more of it could eventually lead to significant, negative side effects,” Schoellhammer says.

Jadhav, meanwhile, explains that nucleic acid-based therapeutics, such as RNAi-based medicines, leverage a platform technology that gives rise to consistent and predictable drug properties. “This is not the case for small molecules, where each individual small molecule compound is completely unique, both in terms of its design elements and its profile as a drug candidate,” he states.

Development of nucleic acid-based therapeutics supports the bio/pharma industry’s shift to precision medicine. For instance, there are examples of nucleic acid-based medicines (e.g., RNAi therapeutics) that are approved to treat rare and ultra-rare genetic diseases for which there were no previously available therapeutic options, points out Jadhav. He has observed the therapeutic landscape of rare diseases dramatically evolve in large part due to the development and availability of genetic medicines, which now have the potential to help patients with more common diseases for which treatment options are limited or inadequate.

Schoellhammer says that, because these medicines are based on genetic sequences, they are highly specific. They can be used to treat rare diseases that are caused by a mutation in our genes. He points out that Biogen’s Spinraza (nusinersen), an antisense therapy for treating spinal muscular atrophy, was a significant accomplishment that has drastically improved the quality of life in patients for whom the disease often presents in newborns and is fatal by age two.

“Beyond presently approved nucleic acid medicines, companies are working on using these therapeutics in combination with CRISPR machinery to enable highly precise edits to genetic signals in patients. In theory, this could one day be used to target a drug for a unique individual,” says Schoellhammer.

Adding to the complex tapestry of nucleic acid-based therapeutics are the different moieties, or species of molecule, within the nucleic acid space. According to Schoellhammer, there are several different types based on their action. Within ASO therapies, for example, there are a variety of strategies to control the “degree” of silencing. There are certain therapeutics, such as Spinraza, for example, that are termed “exon-skipping” because, rather than telling the body to turn off a gene completely, these therapeutics instruct the body to skip only a certain part of a gene when producing the corresponding signal, Schoellhammer explains.

He also emphasizes the existence of microRNA (miRNA), which can have a similar effect to that of silencing therapies, guide RNAs (gRNA), which are used to target a desired gene sequence in the body for editing using CRISPR machinery, and, finally, certain types of RNA medicines that utilize naturally occurring machinery in the body to elicit an editing effect on defective genes. The latter is referred to as transfer RNA (tRNA).

“Beyond this, there is an almost endless further segmentation based on chemical modifications made to the nucleic acid therapy to make it more resilient to degradation by our body or make it more efficient in eliciting its desired effect,” Schoellhammer concludes.

1. Novartis. FDA Approves Novartis Leqvio (inclisiran), First-in-Class siRNA to Lower Cholesterol and Keep it Low with Two Doses a Year. Press Release, Dec. 22, 2021.

Feliza Mirasol is the science editor for 

Articles

Features

The market potential of nucleic acid-based therapies have been pushed into the spotlight following the success of the COVID-19 vaccines.



Ramping Up Nucleic Acid Therapy Development

Analyzing extractables and leachables (E&L) is paramount to ensuring the safety of a drug product and determining any toxicological risks. Examining extractables can help identify potential risks of leachables contaminating or affecting the quality of a drug product. Extractables can be extracted through the use of solvents under certain extraction conditions or can be forced out with high heat without solvents. Extractables may be potential leachables, but not all extractables leach into drug products. Leachables migrate from the container into the drug product or directly to the patients under normal storage or use (1).

Potential sources of leachables include primary packaging components, secondary packaging components, intermediate manufacturing components, or APIs. There are also E&L that can be introduced from the component molding process and can end up becoming a leachable, such as mold release agents or lubricants (1).

Various regulatory guidelines have been published due to the potential safety risks that leachables pose. FDA published a guidance included in the 

 Title 21 that highlights guidelines on drug product containers and closures, such as:

“Drug product containers and closures must not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug beyond the official or established requirements.

“Container closure systems must provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product.

“Drug product containers and closures must be clean and, where indicated by the nature of the drug, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use. Such depyrogenation processes must be validated,” (2).

 General Chapter <665> Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products in 2022, which will come into effect in 2026 (3). The document highlights analytical methods of risk assessment of E&L, including biologic drugs.

The Product Quality Research Institute (PQRI) published two industry guidance documents, titled 

Safety Threshold and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products

Safety Thresholds and Best Demonstrated Practices for Extractables and Leachables in Parenteral Drug Products (Intravenous, Subcutaneous, and Intramuscular)

 (5) that highlight industrial details on how E&L assessments should be performed. The combination of both regulatory and industrial guidance documents provides a fleshed-out guideline for E&L analysis.

Differences between small- and large-molecule drugs

Leachables can interact with small-molecule and large-molecule drugs in different ways, which is a key consideration when testing for E&L in biologics versus small molecules. Biologics can be immunogenic, and a leachable may interact with a protein and trigger an immune response (6). The efficacy of a biologic drug may also potentially be reduced through interactions of leachables with drug molecules through post-translational modification biochemical reactions, such as oxidation, aggregation, or unfolding, explained Lester Taylor, pharma marketing manager at Agilent (7).

Biologic drugs are sensitive and complex. Extractables or potential leachables that may migrate into a drug product have the potential to interact, and therefore, affect the product quality, safety, or stability, explained Fran DeGrazio, vice-president, global scientific affairs and technical services, West Pharma. Additionally, large molecules have greater surface areas, and interactivity can lead to conformational modifications and other interactions that may impact product quality (7).

A main concern for leachables in small-molecule drugs is the specific toxicity/genotoxicity profiles, said Dr. Wayland Rushing, senior scientific advisor at ABC Laboratories. However, with biologics, there is also the concern of the ability of the leachable to interact with the biologic product itself. Many biologics are very sensitive to metal content. As a result, additional monitoring of the metal content may be required (8).

Key components such as semi-volatile organic compounds, non-volatile organic compounds, volatile organic compounds, and metals can be identified during an E&L study. For extractable studies, exaggerated conditions are often used to emulate a “worst-case scenario,” and the data are used to help determine what further studies are needed to mitigate future risks. Examples of analytical techniques used to detect E&L include gas chromatography mass spectrometry, liquid chromatography mass spectrometry, and inductively coupled plasma-mass spectrometry (9). Taking these differences into consideration can help identify the right tests to use for detecting E&L.

1. Yu, X., and Wood, D. Analytical Testing—Extractables and Leachables
Testing for Pharmaceutical Products. 

2. CFR Title 21, 211.94 (Government Printing Office, Washington, DC).

3. USP. General Chapter <665>, Plastic Components and Systems Used to Manufacture Pharmacueitcal Drug Products and Biopharmaceutical Drug Substances and Products.

 Safety Threshold and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products.

 Safety Thresholds and Best Demonstrated Practices for Extractables and Leachables in Parenteral Drug Products (Intravenous, Subcutaneous, and Intramuscular).

6. Moffatt, F. Extractables and Leachables in Pharma-A Serious Issue. (Solvias, accessed March 9, 2023).

7. Siew, A. E&L Risk Assessment for Biologic Drug Products. 

8. Hernandez, R. Special Considerations for Extractables and Leachables Testing in Biological Products. 

9. Thermo Fisher Scientific. Extractables and Leachables: Regulatory Requirements for Vaccine and Biologic Products. (Thermo Fisher Scientific,

E&L analytical testing methods can be determined through pointed consideration of the differences small- and large-molecule drug products.

E&L Analytical Testing Considerations

Adaptive Biotechnologies Corporation announced on April 12, 2023 that it has begun a translational collaboration with Takeda. Adaptive Biotechnologies will use its clonoSEQ Assay to assess minimal residue disease (MRD) to start with the development and commercialization of Takeda’s pipeline of treatments for patients with lymphoid malignancies, according to the press release.

“We are thrilled to enter into a broad translational collaboration with Takeda incorporating the use of our clonoSEQ Assay technology in clinical trials to support the clinical development of groundbreaking oncological therapies,” said Nitin Sood, chief commercial officer, MRD at Adaptive Biotechnologies, in a press release. “MRD is an important measure of whether novel treatments are inducing effective and durable responses for patients, and its use as an endpoint is rapidly growing.”

The first and only next-generation sequencing-based MRD test, clonoSEQ Assay is authorized by FDA for MRD assessment in lymphoid malignancies and is highly accurate, sensitive, and standardized compared to other technologies used for disease burden assessment. It is also the first FDA-cleared 

 diagnostic test service to detect MRD in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia, and blood or bone marrow from patients with chronic lymphocytic leukemia.

“Innovative technology plays a critical role in informing our clinical development plans as we look to bring effective new medicines to patients with hematologic malignancies,” said Christine Ward, Head, Precision and Translational Medicine, Oncology Therapeutic Area Unit (OTAU) at Takeda, in a press release. “This collaboration with Adaptive allows us to further explore the clinical relevance of MRD as we progress our pipeline of investigational medicines.”

MRD status based on Adaptive’s clonoSEQ Assay may be used as an endpoint in certain clinical trials to assess the depth and duration of response to Takeda’s investigational medicines in patients with lymphoid malignancies. The multi-year agreement will cover existing and future programs and adds to Adaptive’s growing list of translational collaborations with pharmaceutical companies, according to the press release.

News

clonoSEQ Assay is authorized by FDA for MRD assessment in lymphoid malignancies and is highly accurate, sensitive, and standardized compared to other technologies used for disease burden assessment.

Adaptive Biotechnologies Announces Collaboration with Takeda for Minimal Residual Disease Measures

On April 12, 2023, Aspect Biosystems and Novo Nordisk A/S announced a collaboration, development, and license agreement to develop bioprinted tissue therapeutics designed to replace, repair, or supplement biological functions inside the body with the aim of delivering a new class of truly disease-modifying treatments for diabetes and obesity, according to a release.

The agreement states that Novo Nordisk will receive an exclusive, worldwide license to use Aspect’s bioprinting technology to develop up to four products for the treatment of diabetes and/or obesity. Meanwhile, Aspect will receive initial payments of US$75 million, including an upfront payment, research funding, and an investment in the form of a convertible note. According to the press release, Aspect is also eligible to receive up to US$650 million in future development, regulatory, commercial and sales milestone payments per product, as well as tiered royalties on future product sales.

“We are thrilled to partner with Novo Nordisk, a global leader and pioneer in the fight against diabetes and chronic diseases, to create breakthrough therapeutics that could transform the lives of millions of people around the world,” said Tamer Mohamed, chief executive officer, Aspect Biosystems, in a press release. “This partnership leverages Aspect’s full-stack tissue therapeutic platform, talented team and bold vision, and reinforces our strategy to create bioprinted tissue therapeutics through partnerships with global industry leaders while also advancing our internal therapeutic pipeline.”

A new platform technology from Aspect may allow for the development of a novel class of cell-based medicine designed to be biologically functional, encapsulated to be immune-protective, and suitable for surgical implantation. For Novo Nordisk, their team has developed expertise to differentiate stem cells into a wide array of cells that may be used to replace damaged and lost cells which could lead to a specific disease, like insulin-producing beta cells in type 1 diabetes, or manufacturing capabilities to produce the cells at scale.

The goal of the partnership is to create implantable bioprinted tissues to replace, repair, or supplement biological functions. Further, these tissues will be designed to be allogeneic, which means the cells used are derived from a single source to increase the practicality of future large-scale manufacturing.

“Novo Nordisk has built strong capabilities when it comes to producing functional and highly pure therapeutic replacement cells at the highest quality and at scale,” said Jacob Sten Petersen, corporate vice president and head of Cell Therapy R&D, Novo Nordisk, in a press release. “Collaborating with Aspect Biosystems adds an important component to our strategy to develop comprehensive cell therapy products. We are excited to co-develop solutions for cell therapy delivery that could lead to life-changing treatments for those living with a serious chronic disease.”

Aspect Biosystems and Novo Nordisk A/S have announced a collaboration, development, and license agreement to develop bioprinted tissue therapeutics. 

Aspect Biosystems, Novo Nordisk Partner to Develop Bioprinted Tissue Therapeutics 

BioChain Institute, a supplier of biosample products and services, recently announced the extension of its spatial multiomics services via partnerships with NanoString Technologies and 10X Genomics. NanoString is a biotechnology company specializing in technology and translational research solutions, while 10X Genomics is a biotechnology company focused on gene sequencing technology.

According to an April 18, 2023 press release, spatial profiling is a technique that reveals the spatial context of RNA and proteins in tissue. BioChain spatial profiling technology uses a three-step process: selecting tissue samples, working with spatial biology scientists to determine which spatial path to use, and running the customized spatial process.

“Our partnerships, combined with our in-house services, make us a full-service provider of spatial biology services,” said Vidyodhaya Sundaram, vice-president of Business Development, BioChain, in the release. “With the technologies now available from BioChain, you can spatially resolve the entire transcriptome or high-plex protein across your tissue sample.”

“Our technology’s advantages include its high multiplexing ability, low hands-on time, and a straightforward procedure,” continued Sundaram. “Our goal is to bring this specialized technology to any researcher or biomedical professional who wants to use it.”

New Technology

BioChain has reached partnerships with NanoString and 10x Genomics to extend its spatial multiomics services. 

BioChain Institute Extends Spatial Multiomics Services

JMI Laboratories, a microbiology laboratory owned by Element Materials Technology, and bioMérieux, a French biotechnology company specializing in diagnostics, announced a six-year partnership in an April 20, 2023 press release. The collaboration will aim to improve microbiology diagnostics in tools to fight antimicrobial resistance (AMR).

According to a company press release, Antimicrobial Stewardship Programs are dependent on rapid, reliable testing that must be continuously evaluated against new and emerging strains of global pathogens. In this partnership, bioMérieux will use data collected through JMI’s microbial surveillance tools to continuously assess AMR results.

“We are excited to partner with bioMérieux on these projects as we appreciate their commitment to improving patient care by providing accurate microbial identification and antimicrobial susceptibility testing results,” said Mariana Castanheira, chief scientific officer of JMI Labs, in the press release. “Our scientists look forward to managing these studies testing challenging organisms, including those carrying important mechanisms of resistance.”

“Through our combined efforts, we can proactively alert the scientific community of potential growing threats and effectively steer antimicrobial research and development,” said François Lacoste, executive vice-president, Research & Development, bioMérieux, in the release.

JMI Laboratories and bioMérieux will work to improve microbiology diagnostics tools.

JMI Laboratories and bioMérieux Enter Antimicrobial Resistance Diagnostics Partnership

FUJIFILM Irvine Scientific, Inc. announced its growth of the BalanCD Chinese Hamster Ovary (CHO) Media Platform portfolio with the addition of two new, chemically defined growth media- BalanCD CHO Perfusion and BalanCD CHO DG44.

The BalanCD CHO media portfolio is designed to ensure maximized growth, viability, and productivity of CHO cell lines via a scalable platform for reliable production and seamless workflow through all stages of development and manufacture, including small-scale shake flasks to large bioreactors. The new additions increase the platform with specific media designed to support DG44 cell lines and perfusion culture platforms for the commercialization of monoclonal antibodies, recombinant proteins, biosimilars, and other biomolecule-based biotherapeutics.

According to the press release, the BalanCD CHO Perfusion medium is a chemically defined, animal component-free medium optimized to deliver robust cell growth and productivity in steady-state, perfusion CHO culture. This medium is verified to meet industry performance standards for perfusion culture conditions including volumetric productivity (VP), cell specific perfusion rates (CSPR), and vessel volumes per day (VVD).

Additionally, BalanCD CHO Perfusion is a complete, ready-to-use medium that is adaptable and scalable for a variety of perfusion culture platforms, including perfusion mimic and perfusion-capable bioreactors. It is designed for high cell density conditions and to deliver high titers, and BalanCD CHO DG44 medium is specifically created for optimal growth and productivity of CHO DG44 cell lines. It also supports both batch and fed-batch cultures, which makes it highly compatible with a wide range of culture platforms and transfection reagents.

“With CHO cells being such a pivotal part of many biotherapeutic development and manufacture pipelines, FUJIFILM Irvine Scientific designed the BalanCD CHO platform to deliver consistent, high-quality growth of CHO cells and production of biomolecules to accelerate the development and manufacture of life-saving therapies for patients around the world and achieve more cost-efficiencies within biotherapeutic manufacturing,” said Erik Vaessen, chief business officer, FUJIFILM Irvine Scientific, in a press release.

The BalanCD CHO media portfolio is designed to ensure maximized growth, viability, and productivity of CHO cell lines.

New Expansion for BalanCD CHO Media Platform Portfolio for Bioprocessing 

Lonza announced on April 4, 2023 an agreement with ABL Bio, a Korean biologics company with a focus on bispecific antibodies for immune-oncology and neurodegenerative diseases. The collaboration agreement between the two companies supports the development and manufacturing of ABL Bio’s new bispecific antibody product.

Under the agreement, Lonza will provide ABL Bio with an end-to-end solution and an integrated offering to support the bispecific antibody candidate from DNA to potential investigational new drug (IND) application. ABL Bio will also gain access to Lonza’s DNA-to-IND program, which is designed to support biotech companies in realizing the full potential of bispecific drug candidates, accelerating their path to clinic and developing a robust and scalable manufacturing process.

“With the biologics pipeline evolving towards more complex protein formats, bi- and multi-specific molecules are a growing part of Lonza’s portfolio,” said Jean-Christophe Hyvert, president of biologics, Lonza, in a company press release. “For more than 35 years, our teams have built extensive experience and capabilities in this area, and we are committed to supporting our customers on their unique journey to IND. This collaboration will provide ABL Bio with greater flexibility and speed on the path to commercialization. We look forward to working together to bring this innovative therapeutic antibody candidate one step closer to patients.”

Lonza and ABL Bio are collaborating on the development and manufacture of bispecific antibody product. 

Pharmaceutical Technology's In the Lab eNewsletter, May 2023