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

Many drug molecules, particularly biologics and vaccines, are unstable at room temperature when formulated in aqueous solutions and must be frozen or lyophilized (freeze-dried) to allow their storage and shipment. Freezing and freeze-drying involve harsh conditions that can degrade the active ingredients. Cryoprotectants and lyoprotectants are excipients used in drug product formulations to ensure that safe and efficacious products are obtained following these processes. As such, the quality of those excipients can have a direct impact on the final stability and performance of frozen and lyophilized drugs and vaccines, as explained independently by two industry experts.

Excipients used as cryoprotectants and lyoprotectants serve mainly to protect the drug substance in a formulation from degradation or disassociation during the freezing or freeze-drying process, according to Christy Eatmon, global subject matter expert, sterile drug products, in the pharma services business of Thermo Fisher Scientific. Lyoprotectants also provide a bulking effect so that the resulting dried cakes can be readily reconstituted.

Most cryoprotectants are monosaccharides (sugars), polysaccharides, or polyols, observes Virginie Le Brun, associate director of formulation development for Lonza Drug Product Services. There are limited options, she adds, because only certain excipients are suitable for use in drugs for human use, particular
 parenteral applications.

The selection of the best excipient or combination of materials and their quantity(ies) is dependent on the molecule type, according to Eatmon. She recommends the use of a design-of-experiment (DoE) approach to identify which materials work best with the target drug product.

Take a structured approach to development

Ideally, formulation compositions for drug products that must be frozen or lyophilized should be kept simple. “Whenever possible, just one excipient with sufficient ability to protect, and if necessary act as a bulking agent, should be selected,” Le Brun says. However, she adds that there might be situations where a combination is needed to achieve the most stable formulation conditions.

During formulation development, it is important, observes Heiko Nalenz, associate director of process development for Lonza Drug Product Services, to take a structured approach to development, addressing process challenges during early formulation selection. “Excipient selection should be based on the intended storage conditions and/or compatibility with the freeze-drying process. For this purpose, the thermally induced transitions of the complete product matrix (e.g., glass-transition temperature and collapse temperature) should be characterized,” he explains.

Eatmon agrees, once again underscoring the value of performing selective DoE studies to determine which excipients are most successful for the formulation and product under evaluation. “Characterization is important to understand and develop key parameters of the lyophilization cycle. For example, with a small molecule, it is important to understand whether the molecule is crystalline or amorphous. With that information in hand, the eutectic point or glass-transition temperature should be determined to enable excipient selection,” she comments.In the case of large molecules or more complex formulations, such as dispersions, Eatmon notes that the need for a combination of excipients is more likely.

Quality and purity can have multiple impacts

As with APIs, the quality and purity of lyo/cryoprotectants used in formulations that are frozen or lyophilized is important. “Impurities in materials may cause slight differences in critical attributes, which can lead to incomplete freezing or poor sublimation during the drying process,” Eatmon says. They may also negatively affect the product’s stability in the frozen or freeze-dried state, according to Nalenz. For crystallizing excipients, he points to the potential of varying impurity profiles to increase or decrease their propensity to crystallize, which might impact the quality of the drug component if it ends up in the final product in a non-desirable state.

The biggest potential impact of poor-quality cryo/lyo excipients is, according to Eatmon, for the resulting frozen or lyophilized product to fail to meet acceptance criteria, resulting in rejection of the material. “Robust quality systems should prevent the use of non-compliant materials, but if the quality issue is unexpected, timelines may be delayed while a replacement is sourced. Plans should be in place in advance to efficiently manage this type of scenario,” Eatmon emphasizes.

In addition, variability in the properties of excipients can also create challenges. “Even excipients in compliance with compendial quality specifications may have some variability in their properties or impurity profiles that may impact cryo/lyoprotective properties,” Nalenz remarks. This variability for many cryo/lyoprotectants can be attributed to the fact that they come from plant sources (e.g., starch), according to Le Brun.

Suppliers can help avoid such issues by deeply characterizing the cryo/lyo excipients they produce and obtaining knowledge of how variability might impact their products’ cryo-protective and other properties, observes Nalenz. Drug manufacturers, meanwhile, can for lyophilized products perform lyo cycle tests using different lots of lyoprotectants to ensure that batch-to-batch variability is accounted for in the final formulation, according to Eatmon. She also recommends that conservative measures be taken when developing lyophilization cycles to account for some variability in excipients, upstream drug substances, and drug-product manufacturing processes.

Excipient sourcing and characterization crucial

Appropriate sourcing of any type of excipient is essential to ensuring security of supply and the use of high-quality, compliant materials. For instance, Eatmon stresses the importance of sourcing materials that are intended for pharmaceutical use rather than nutraceutical- or food-grade materials. She also indicates that excipients classified as ultra-pure or low bioburden are preferable for use in injectable products, which comprises most frozen and freeze-dried products. In addition, given the potential for variability in excipient batches, Le Brun emphasizes the importance for formulators of understanding that variability and its impact on the properties of the drug product before selecting a specific excipient supplier.

While common cryo/lyoprotectants and bulking agents are well understood, used in a variety of commercial products, have multiple high-quality sources, and comply with a variety of compendia, there are limited
numbers of them suitable for parenteral applications, according to Eatmon. Other than the challenges related to impurities and variability, Le Brun comments that the limited options can represent a significant hurdle, particularly for newer modalities.

It is hoped that the FDA’s Pilot Program for the Review of Innovation and Modernization of Excipients (referred to as PRIME), which was launched in September 2021 (1), will lead to a regulatory pathway for approval of novel excipients and innovation in the excipients space, including new cryo- and lyoprotectants.

FDA. Center for Drug Evaluation and Research Office of New Drugs Novel Excipient Review Pilot Program. 

Cynthia A. Challener, PhD, is a contributing edtior to 

Batch-to-batch variability and impurities present critical challenges.

Cryo/Lyoprotectants Quality Challenges

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.”

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

In April 2023, Ginkgo Bioworks announced two major moves that bolster its R&D and drug discovery services. The first move is the acquisition of the adeno-associated virus (AAV) capsid discovery and engineering platform assets of US-based gene therapy company, StrideBio. The second move is the formation of a partnership with the Wisconsin Alumni Research Foundation (WARF) to discover and develop next-generation chimeric antigen receptor T cell (CAR-T) cell therapies.

According to an April 5, 2023 company press release, Ginkgo will incorporate the capabilities and intellectual property (IP) it gains from the StrideBio acquisition into its end-to-end AAV gene therapy development platform. This combination will allow for the use of new tools that can effectively target many different tissue types and potentially improve the safety profile of future gene therapies. Ginkgo is also receiving StrideBio's existing library of capsids, which includes advanced candidates that have been extensively tested in large animal models and which are now available for licensing and broader partnership.

Also under the agreement, Ginkgo will gain the IP and data for StrideBio's lead preclinical asset for arrhythmogenic right ventricular cardiomyopathy , a rare genetic heart disease. Ginkgo plans to sell or outlicense this preclinical asset to a commercial partner. The transaction includes a secondary close that is scheduled upon transfer of certain additional in-license agreements to Ginkgo. Financial details of this deal were not disclosed.

"The StrideBio team has built a deep pipeline of AAV capsids and libraries to address critical challenges facing clinical gene therapy with a focus on reducing vector dose and improving safety by limiting off-target biodistribution," said Aravind Asokan, co-founder of StrideBio, in the press release.

"Combining Ginkgo's engineering and discovery capabilities in enzymes, regulatory elements, and capsids enables a holistic approach to designing an AAV gene therapy, so that we can support our partners across the entire process of designing the viral vector," said Narendra Maheshri, head of Mammalian Engineering at Ginkgo, in the press release. "We are thrilled to integrate the STRIVE platform and know-how into our foundry to augment our capabilities in capsid engineering, and we look forward to continuing to expand our existing end-to-end capabilities in AAV discovery and manufacturing."

Next-gen cell therapy discovery and development

In its collaboration with WARF, which supports research at the University of Wisconsin-Madison, Ginkgo will offer its proprietary high-throughput combinatorial CAR discovery and screening platform to researchers at WARF. The aim of the collaboration is to discover next-generation GD2 CAR-T cell therapies that have improved persistence, proliferation, fitness, and other functional properties. The goal of developing these next-gen cell therapies is to improve the efficacy of treatment for solid tumors.

According to an April 13, 2023 press release, Ginkgo will collaborate with University of Wisconsin-Madison researchers Krishanu Saha, professor at the University of Wisconsin-Madison and principal investigator (PI), and Christian Capitini, co-PI. Saha's lab is focused on developing next-generation cell engineering techniques to advance human therapeutics, while Capitini is a pediatric oncologist who has extensive clinical experience with CAR-T cell therapies. Capitini also served as a site PI for the clinical trial that led to the first FDA approval of a CAR-T cell therapy.

Under this collaboration, Ginkgo will design and characterize novel intracellular signaling domains using its pooled CAR screening platform. These signaling domains are intended to prevent the exhaustion of T cells in the GD2 solid tumor context, according to Ginkgo in the press release. Any novel designs will be validated via high throughput 

 murine models. Ginkgo and WARF also plan to collaborate on developing a pooled 

 screening platform to further advance the discovery of novel CARs.

"Ginkgo's high throughput screening method has proven successful in enabling massively parallel testing of CAR designs and has already led to the discovery of new intracellular domains (ICD) combinations," said Saha in the press release. "By partnering with Ginkgo, we aim to unlock the potential to transform patient outcomes and reimagine the future of solid tumor cancer treatment."

"This collaboration represents a fantastic opportunity to demonstrate the potential value of pooled CAR screening approaches directly in the context of devastating diseases [such as] early childhood cancers," said Narendra Maheshri, head of Mammalian Engineering at Ginkgo, in the release. "It's especially exciting to work with pioneers [such as] Professors Saha and Capitini, who have pushed R&D boundaries in the laboratory and whose approach is thoroughly grounded in the translation of their findings for clinical impact."

Ginkgo Bioworks has acquired StrideBio's AAV capsid discovery and engineering platform and has formed a partnership with WARF for development of next-gen cell therapies.

Ginkgo Bioworks Acquires AAV Capsid Technology and Forms Partnership for Next-Gen CAR-T Cell Therapies

AnaBios, a US-based preclinical contract research organization, has acquired Cell Systems, a US-based human primary cell and cell culture media company, in a deal that will bolster AnaBios’ human tissue and cells portfolio. Financial terms of the transaction were not disclosed.

The acquisition will help scientists expedite drug discovery and further understanding of cell biology through access to an expansive array of biologically relevant tools, AnaBios announced in an April 4, 2023 press release.

Cell Systems’ offering includes a variety of human primary cells, including endothelial cells from the brain, liver, kidney, eye, and lung. The company’s liver sinusoidal endothelial cells were used in a recent pivotal study of a novel liver-chip model that was said to have rigorously validated the use of the primary cells for microfluidics application in accordance with industry standards set by the International Consortium for Innovation and Quality in Pharmaceutical Development, according to the press release.

AnaBios’ advanced technologies provide human tissue samples, cells, and services for the pharmaceutical industry and academic laboratories globally. Human primary cells and tissues are important for providing clinically relevant data to increase the success rate of drug development.

“Cell Systems has decades of experience supplying our … human primary cells to pharma/biotech companies and universities around the world that enable translational research using 2D and 3D models, microfluidic devices, and in organ-chip technology. Our primary cells have been instrumental in research of the blood-brain-barrier, liver biology, kidney function, respiratory biology, and much more,” said Jesse Damm, CEO of Cell Systems, in the press release.

“AnaBios is extremely excited to provide Cell Systems’ primary cells to researchers globally and further enhance the landscape of translational research,” said Andre Ghetti, CEO of AnaBios, in the release. “By maximizing the synergies between our offerings and expertise and Cell System’s human primary cells and media, we will provide enhanced translational tools and reagents to academic, pharmaceutical, and biotech researchers and optimize their research programs through enhanced human insights.”

The acquisition of Cell Systems will bolster AnaBios’ portfolio of human tissue and cells for use in drug discovery.

AnaBios Acquires Cell Systems, Expands Human Cell Portfolio for Drug Discovery

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.

New Technology

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

BioPharm International's BP Elements, May 2023