A: Patients are already receiving treatment using novel gene and cell therapies. The field is advancing rapidly and this year we have seen CAR-T therapies, RNAi therapies, and gene therapies become commercially available in the US. Additionally, there’s a bolus of clinical studies, in particular mRNA therapies and mRNA vaccines, that would yield yet more new genetic medicines. As more therapies for a range of indications become approved in the US and globally, the clinical use of these types of treatments will grow. The first clinical trials using CRISPR have been announced and patients are likely to be dosed shortly. As these platform technologies begin to prove themselves out, we will see an acceleration of new therapies becoming available.

A: Nanoparticle-based drug delivery is a key enabling technology for a wide range of genetic medicines, including for small RNA, mRNA, CRISPR, and many others. Nanoparticle technologies address a common challenge facing genetic medicines, namely the delivery of these macromolecules to the site of disease and into cells. As such, there is significant industry and academic innovation occurring in delivery technologies, and the platforms are rapidly becoming clinical realities. For example, the recent FDA approval of Patisiran, a lipid nanoparticle based RNAi therapy and the first approved RNAi therapy, is a validation that lipid nanoparticles are safe and effective. Already, there are clinical trials ongoing for lipid nanoparticle-based mRNA therapies and mRNA vaccines and there are companies using LNPs to deliver CRISPR components in late stages of preclinical research. So in both the near and far future, I see nanoparticle technologies playing an important role in enabling the clinical success of precision medicine and hence impacting patient care. Further in the future I envision personalized medicines being manufactured at the point of care where a disease is diagnosed, the molecular origin of the disease identified through sequencing, and a molecularly tailored medicine is designed and made for individual patients and their specific needs. Nanoparticle technologies will enable such individualized medicines as they are manufactured synthetically on demand, which is very different than cell based manufacture of proteins or manufacturing of viral delivered gene therapy.

A: The three pillars of clinical success are always quality, safety and efficacy. Successful strategies have to be built at all stages of development. Nanomedicines are a sophisticated drug product, whereby the excipient (nanoparticle delivery systems) can have as large or greater impact on quality, safety and efficacy, as the active pharmaceutical ingredient (i.e. mRNA, cas9, etc.). So to be successful, a plan needs to be built in place around all aspects of the drug product. Further, matching the indication with the technical advantages of the technology can have a significant impact on the success of a new therapeutic modality. For instance, it is important to consider how the disease manifests itself genetically and if it is a Mendelian or a complex disease, what tissues the disease occurs in, how often it will need to be dosed, etc. Often the therapeutic modalities are being tested for the first time (i.e. CRISPR gene editing), and it is important to minimize compounding technical risk.

A: As we see the new genetic medicine modalities become proven in the clinic, we anticipate significant continued investment into these areas. We are already seeing huge capital investment by pharma and the venture community into these modalities, as they hold the promise to treat disease at its root genetic cause. Additionally, there is a diverse set of genetic medicine technologies, from siRNA and ASOs for gene silencing, mRNA for protein expression, DNA constructs for persistent expression, genomic editing for permanent change, and a variety of powerful cell therapy approaches requiring ex vivo cell manipulation. The pace of innovation is unlike anything we have seen in the past, and deficits faced by one method are an advantage for another.

One major challenge however, is turning these early concepts into clinical products. It is important that as these drug products are translated from bench scale development to the clinic, they are consistent and maintain the performance seen as what you’ve built your data and evidence of performance around. The field has seen many failures of translating programs that demonstrate great performance at the bench scale, but could not be translated into clinical setting. At PNI, we have focused on this concept specifically, to create manufacturing technologies that allow seamless scale up of formulations from discovery to the clinic, and to provide the technical expertise to do this well. This ensures reliable results and high quality formulations throughout the development process.

A: The community should continue to promote and share knowledge on how to successfully develop these exciting new classes of drugs. The potential of these drugs is immense, but they often comprise the combination of multiple disparate technologies to be successful. It is also important that the academic and industry community maintains a fluid collaborative environment, where multiple technologies and areas of expertise can be shared and combined.

Nanotechnologies present new opportunities for advancing medical science and disease treatment in human health care. At PNI, we strive to create and drive knowledge into the community through our Nanomedicine Innovation Network (NIN). The purpose of the Nanomedicine Innovation Network is to provide an overview of the latest research and developments and highlight the remarkable work happeninging to foster learning and inspiration. We are committed to an exchange of ideas and cultivation collaborations with the recent establishment of five global NIN Network sites located in the University of Strathclyde, Evonik’s Darmstadt Site, Harvard Medical School ncRNA Core Facility, PNI’s Vancouver Headquarters and in our San Francisco office all that will conduct workshops and onsite training.

A: As mentioned before, PNI provides a technology platform, expertise and services that address formulation and manufacturing challenges at all stages of drug development. Most of the top organizations in CRISPR, RNA, and gene therapies are using our technology and services to develop their products for targeted or personalized medicine. Essentially, we have the technology and the expertise needed to develop our own therapeutics in this space but we choose to leverage this to help numerous organizations and their personalized medicine programs be successful, and in so doing, we believe we have a greater impact on the field.

PNI’s mission is to accelerate the creation of transformative medicine that significantly impacts human well being. We are proud of the impact we have made in the field and look forward to working with our users to bring these important medicines to patients.

A: It is a tremendously exciting time in the life sciences. Similar to the digitization of genomic information through sequencing, we are seeing a digitization of therapeutic design through genetic medicines. The impact this will have on the human condition will be larger than anything we have seen in medicine, and provides a near infinite potential for us as scientists, industry leaders, and citizens.