With multiple FDA-approved treatments and dozens more in clinical trials, gene therapy is rapidly becoming a cornerstone of modern medicine. But as the field matures, the industry faces a growing logistical challenge: how to produce gene therapies at scale, quickly and cost-effectively, without compromising quality.
One of the biggest obstacles lies in the manufacturing of recombinant adeno-associated viruses (rAAVs), the viral vectors that deliver therapeutic genes to cells. Standard production techniques often generate a mix of full capsids (which contain the therapeutic genome) and empty ones (which don’t). Separating these is critical—only full rAAVs have clinical benefit—but current methods rely on time-consuming purification steps.
Several analytical methods have been explored to measure and optimize the ratio of full-to-empty particles (F/E ratio) during rAAV production. Common techniques include ultraviolet absorbance spectroscopy, which estimates DNA content by comparing A260/A280 ratios, and enzyme-linked immunosorbent assays (ELISAs) coupled with quantitative PCR. While useful, these methods often require purified samples, rely on reference standards, and are limited in their ability to distinguish closely related particle types like partially filled or overpackaged capsids.
In essence, no method has yet offered a quick, scalable, and accurate solution for assessing rAAV quality at the point of production—until perhaps now. A new study from researchers at the University of Osaka, published in Analytical Chemistry, introduces a promising alternative. The team demonstrated that mass photometry—a label-free, single-particle technique based on interference scattering microscopy—can accurately distinguish between full and empty rAAV particles in crude cell lysates and conditioned media, with no need for prior purification. This could help speed up the process by detecting and quantifying components of the “delivery system” for therapeutic genes.
This matters because mass photometry operates differently from conventional assays. It detects binding and unbinding events between molecules and a glass surface, measuring their mass with high sensitivity. The study found that most impurities from host cells tend to bind strongly to the glass surface, while rAAV particles (especially full ones) are more likely to unbind, creating a clean, quantifiable signal even in complex biological mixtures.
By focusing on these unbinding events, the researchers were able to directly calculate the full-to-empty particle ratio and estimate the genomic titer of rAAVs in unpurified samples. Their measurements were validated with digital PCR and analytical ultracentrifugation and showed high accuracy across three widely used AAV serotypes (AAV2, AAV8, and AAV9). Mass photometry also enabled the team to track viral vector production over time in both cell lysates and conditioned media.
In the context of this week’s ASGCT Annual Meeting, where much of the conversation is focused on scalability, safety, and process development, the implications are timely. A rapid, small-sample technique that bypasses purification could significantly streamline vector manufacturing, reduce costs, and accelerate quality control workflows.
While mass photometry may not replace more detailed structural or biochemical analyses, its utility as a real-time, early-stage screening tool is clear. For developers racing to bring gene therapies from bench to bedside, this approach could offer a much-needed edge.
As gene therapy continues to expand its clinical reach, innovations like this help ensure the field is not just scientifically exciting—but industrially viable.
Read more about recent advances in the development of vector technology here.
The post Mass Photometry Speeds Up Gene Therapy Manufacturing—No Purification Needed appeared first on GEN - Genetic Engineering and Biotechnology News.
One of the biggest obstacles lies in the manufacturing of recombinant adeno-associated viruses (rAAVs), the viral vectors that deliver therapeutic genes to cells. Standard production techniques often generate a mix of full capsids (which contain the therapeutic genome) and empty ones (which don’t). Separating these is critical—only full rAAVs have clinical benefit—but current methods rely on time-consuming purification steps.
Several analytical methods have been explored to measure and optimize the ratio of full-to-empty particles (F/E ratio) during rAAV production. Common techniques include ultraviolet absorbance spectroscopy, which estimates DNA content by comparing A260/A280 ratios, and enzyme-linked immunosorbent assays (ELISAs) coupled with quantitative PCR. While useful, these methods often require purified samples, rely on reference standards, and are limited in their ability to distinguish closely related particle types like partially filled or overpackaged capsids.
In essence, no method has yet offered a quick, scalable, and accurate solution for assessing rAAV quality at the point of production—until perhaps now. A new study from researchers at the University of Osaka, published in Analytical Chemistry, introduces a promising alternative. The team demonstrated that mass photometry—a label-free, single-particle technique based on interference scattering microscopy—can accurately distinguish between full and empty rAAV particles in crude cell lysates and conditioned media, with no need for prior purification. This could help speed up the process by detecting and quantifying components of the “delivery system” for therapeutic genes.
This matters because mass photometry operates differently from conventional assays. It detects binding and unbinding events between molecules and a glass surface, measuring their mass with high sensitivity. The study found that most impurities from host cells tend to bind strongly to the glass surface, while rAAV particles (especially full ones) are more likely to unbind, creating a clean, quantifiable signal even in complex biological mixtures.
By focusing on these unbinding events, the researchers were able to directly calculate the full-to-empty particle ratio and estimate the genomic titer of rAAVs in unpurified samples. Their measurements were validated with digital PCR and analytical ultracentrifugation and showed high accuracy across three widely used AAV serotypes (AAV2, AAV8, and AAV9). Mass photometry also enabled the team to track viral vector production over time in both cell lysates and conditioned media.
In the context of this week’s ASGCT Annual Meeting, where much of the conversation is focused on scalability, safety, and process development, the implications are timely. A rapid, small-sample technique that bypasses purification could significantly streamline vector manufacturing, reduce costs, and accelerate quality control workflows.
While mass photometry may not replace more detailed structural or biochemical analyses, its utility as a real-time, early-stage screening tool is clear. For developers racing to bring gene therapies from bench to bedside, this approach could offer a much-needed edge.
As gene therapy continues to expand its clinical reach, innovations like this help ensure the field is not just scientifically exciting—but industrially viable.
Read more about recent advances in the development of vector technology here.
The post Mass Photometry Speeds Up Gene Therapy Manufacturing—No Purification Needed appeared first on GEN - Genetic Engineering and Biotechnology News.