# A Multipoint Injection Technology for Highly Efficient Convection-Enhanced Delivery of Gene-Based Therapeutics

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $605,166

## Abstract

PROJECT SUMMARY/ABSTRACT
The rapid development of novel molecular therapies for neurological disorders has led to a rapid progress in the
translational pipeline: to date, there are multiple active clinical trials and one therapy has already been approved
by FDA. Most commonly, gene therapies rely on Adeno Associated Virus (AAV) due to its safety, transduction
efficiency, and long-term gene expression. In programs where AAV delivers cargo to restricted brain regions, it
requires direct intracerebral injection. For instance, in Parkinson’s (PD) and Huntington’s disease (HD) a deep
forebrain nucleus known as the putamen is often the target. However, complete coverage and efficient
transduction of the entire putamen with AAV is challenging. Current delivery methods require multiple
stereotactic injections through a single cannula. The serial nature of these injections is not only time consuming,
but adds the risks of multiple brain penetrations and iterative displacement of the target. Furthermore, even in
the most successful cases, the transduction efficiency of gene vectors delivered via single point injections is <
50%, which ultimately severely affects therapeutic efficacy. Beyond gene therapy, inadequate delivery is also
critically affecting the efficacy of a number of other therapies relying on direct brain delivery, such as chemical
and molecular platforms for treatment of glioblastoma. Inspired by this critical unmet need, we have developed
a novel device for highly efficient intracerebral injections that minimizes risks. The Multipoint Injection Technology
(MINT) consists in a central catheter integrating three moveable microcannulas connected to a central actuation
mechanism for precise targeting and positioning, as well as maximization of volume coverage. Compared to
current single cannula systems, MINT allows simultaneous injections from multiple microcannulas, thus
eliminating the need for serial trajectories and potentially significantly reducing complexity, duration, and cost of
the surgery. Furthermore, MINT is compatible with magnetic resonance imaging (MRI) and can be seamlessly
integrated with the current surgical workflows based on MR-guidance and monitoring. Finally, the radial
configuration and the multiple injections sites along each microcannula result in a more uniform distribution of
the infusate in the tissue, thus maximizing the volume distribution and enabling targeting of different brain
regions. In this project, we will advance this highly efficient intracerebral injection technology by validating it for
MR-guided injections with benchtop tests and in vivo in non-human primates. Upon completion of this project,
we expect to move the field forward by generating and validating a new delivery device that will significantly
improve coverage, while reducing surgical time and number of transcortical trajectories. Overall this proposal
will establish the future clinical potential of the multipoint injection device as a potenti...

## Key facts

- **NIH application ID:** 10374904
- **Project number:** 5R01NS117756-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** TIMOTHY H LUCAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $605,166
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374904

## Citation

> US National Institutes of Health, RePORTER application 10374904, A Multipoint Injection Technology for Highly Efficient Convection-Enhanced Delivery of Gene-Based Therapeutics (5R01NS117756-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10374904. Licensed CC0.

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